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- The Company of Biologists
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- © 2021 The Company of Biologists. All rights reserved.
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- 0021-9533
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- 0021-9533
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- 10.1242/jcs.028308
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Abstract
Commentary 2167 No strings attached: the ESCRT machinery in viral budding and cytokinesis Bethan McDonald and Juan Martin-Serrano* Department of Infectious Diseases, King’s College London School of Medicine, Guy’s Hospital, London, SE1 9RT, UK *Author for correspondence (e-mail: [email protected]) Journal of Cell Science 122, 2167-2177 Published by The Company of Biologists 2009 doi:10.1242/jcs.028308 Summary Since the initial discovery of the endosomal sorting complex the site of viral budding, ESCRT proteins are also recruited required for transport (ESCRT) pathway, research in this field to the midbody – the site of release of daughter cell from mother has exploded. ESCRT proteins are part of the endosomal cell during cytokinesis. In this Commentary, we describe recent trafficking system and play a crucial role in the biogenesis of advances in the understanding of ESCRT proteins and how they multivesicular bodies by functioning in the formation of vesicles act to mediate these diverse processes. that bud away from the cytoplasm. Subsequently, a surprising This article is part of a Minifocus on the ESCRT machinery. For role for ESCRT proteins was defined in the budding step of further reading, please see related articles: ‘The ESCRT machinery at some enveloped retroviruses, including HIV-1. ESCRT proteins a glance’ by Thomas Wollert et al. (J. Cell Sci. 122, 2163-2166) and are also employed in this outward budding process, which ‘How do ESCRT proteins control autophagy?’ by Tor Erik Rusten and results in the resolution of a membranous tether between the Harald Stenmark (J. Cell Sci. 122, 2179-2183). host cell and the budding virus particle. Remarkably, it has recently been described that ESCRT proteins also have a role Key words: Abscission, Cytokinesis, ESCRT, HIV-1, L-domain, in the topologically equivalent process of cell division. In the Retroviral assembly same way that viral particles recruit the ESCRT proteins to Introduction From yeast to humans – assembly and function of the The endosomal sorting complex required for transport (ESCRT) ESCRT machinery proteins were initially identified in Saccharomyces cerevisiae as The ESCRT proteins make up four protein complexes termed class E vacuolar protein sorting (Vps) gene products (Katzmann ESCRT-0, ESCRT-I, ESCRT-II and ESCRT-III. This machinery et al., 2002; Raymond et al., 1992). Since then, the majority of assembles on the endosomal membrane and, through a series of work aimed at characterising these proteins has focused on ubiquitin-interacting elements, identifies ubiquitin-labelled receptors, determining their function in the sorting and degradation of which are destined for lysosomal degradation. Sorting of these ubiquitylated membrane receptors in the late endosome-lysosome receptors into the intralumenal vesicles (ILVs) of MVBs allows pathway. Several models have been proposed to explain the subsequent exposure to lysosomal acidic hydrolases when the MVBs association of the different complexes and the mechanics of fuse with the lysosome. Studies in yeast suggest that the ESCRTs are membrane deformation and vesicle formation (Hurley and Emr, sequentially recruited to the endosomal membrane through various 2006; Nickerson et al., 2007). Surprisingly, work carried out more protein and lipid interactions (Burd and Emr, 1998; Gill et al., 2007b; recently has revealed additional functions of the ESCRT proteins Katzmann et al., 2003; Stahelin et al., 2002). Recent structural studies in viral budding and cytokinesis. Now, the question to address is: have provided a better understanding of how ESCRT-I and ESCRT-II what aspects of ESCRT function are required for these processes? are assembled, and of their interactions with ubiquitylated cargo (Gill It is not known whether viral budding requires the same membrane et al., 2007a; Kostelansky et al., 2007; Kostelansky et al., 2006; Pineda- deformation activity as is involved in the biogenesis of Molina et al., 2006; Teo et al., 2006; Teo et al., 2004a; Teo et al., multivesicular bodies (MVBs), or whether this function is provided 2004b), areas that have been expertly reviewed (Hurley and Emr, 2006; by the oligomerisation of the membrane-associated viral Gag Williams and Urbe, 2007). Finally, ESCRT-III recruits the AAA- proteins (Gottlinger, 2001). Likewise, during cytokinesis, the ATPase Vps4, a key enzyme that is required for ESCRT function and daughter cell is formed by massive membrane remodelling, disassembly. Although ESCRT proteins and the protein-protein involving the contraction of an actomyosin ring around the cell interactions of the ESCRT pathway are remarkably conserved from perimeter, rather than the ‘budding’ of a nascent cell from the yeast to humans (Bowers et al., 2004; Martin-Serrano et al., 2003b; plasma membrane. Despite differences in the processes of MVB von Schwedler et al., 2003), some differences are evident. For biogenesis, viral-particle release and cytokinesis, it is clear that example, ESCRT-II is required for MVB biogenesis in yeast, but its they have in common the requirement for a membrane-scission functional significance in humans is still under debate (Bowers et al., event for the release of the progeny vesicle, virion or daughter 2006; Langelier et al., 2006; Malerod et al., 2007). cell (Fig. 1). Here, we explore the evidence supporting the role of ESCRT proteins in membrane scission and the possibility that The core ESCRT machinery different ESCRT subunits are required for differential ESCRT ESCRT-III is thought to provide the core activities of membrane functions. deformation and scission, and is required for all known ESCRT Journal of Cell Science 2168 Journal of Cell Science 122 (13) found in CHMP3 (Whitley et al., 2003) and CHMP4 (Lin et al., 2005) and a myristyl group in CHMP6 (Yorikawa et al., 2005). However, the C-terminal domains are free to recruit additional ESCRT-binding partners. CHMP proteins bind to microtubule- interaction and trafficking (MIT)-domain-containing proteins, such as VPS4 and the activator protein LIP5, via a MIT-interaction motif (MIM) at their C-termini (Agromayor and Martin-Serrano, 2006; Azmi et al., 2008; Nickerson et al., 2006; Obita et al., 2007; Scott et al., 2005b; Shim et al., 2008; Stuchell-Brereton et al., 2007; HIV-1 budding Tsang et al., 2006; Xiao et al., 2008). The connection between the VPS4-LIP5 complex and the CHMP4-CHMP6 subcomplex occurs via a slightly different mechanism, as these CHMP proteins do not Nucleus ILV contain the conventional MIM. Instead, Kieffer et al. have reported Abscission an alternative interaction that occurs between CHMP6 and the MIT MVB biogenesis domain of VPS4 through a region of CHMP6 that they term an ‘MIM2 element’ (Kieffer et al., 2008). Functional MIM2 elements have also been identified in CHMP4 and the regulatory protein IST homolog (hIST1) (described below) (Bajorek et al., 2009). Fig. 1. A diagram illustrating topologically equivalent ‘budding’ events for VPS4 enzymes form oligomeric complexes on endosomal which the ESCRT machinery is required. The formation of intralumenal membranes (Babst et al., 1998; Scott et al., 2005a); these vesicles (ILVs) within multivesicular bodies (MVBs), viral budding and abscission during cytokinesis all require the resolution of a cytoplasm-filled complexes are comprised of two hexameric (Yu et al., 2008) or membranous tether. heptameric (Hartmann et al., 2008) rings. In yeast, Vta1 (human LIP5) stimulates the ATPase activity of Vps4 (Azmi et al., 2006; Lottridge et al., 2006) and promotes the assembly of the double functions in yeast and humans. Some of the pioneering work in this ring structure (Xiao et al., 2008). VPS4 activity is also regulated field suggested that ESCRT-III assembles as an insoluble lattice on by several proteins, including ESCRT-III itself (Azmi et al., 2008) the endosomal membrane and mediates membrane deformation and the newly identified ESCRT-related protein Ist1 (Dimaano through a mechanism involving Vps4. Deletion of ESCRT-III et al., 2008; Rue et al., 2008). Ist1 forms a subcomplex with Did2 components, or the expression of catalytically inactive Vps4 (human CHMP1A or CHMP1B) and, in humans, hIST1 interacts mutants, prevents the normal degradation of endosomal cargo and with LIP5, VPS4 and other MIT-domain-containing proteins via causes the accumulation of aberrant endosomes (Babst et al., 2002; two MIMs located at the extreme C-terminus (Agromayor et al., Babst et al., 1997; Babst et al., 1998; Bishop and Woodman, 2000). 2009; Bajorek et al., 2009). Studies in yeast initially suggested A function in membrane scission is also suggested by the finding that the Ist1-Did2 complex is a positive modulator of Vps4 through that these large aberrant endosomes lack internal vesicles (Babst the stabilisation of its interaction with ESCRT-III at the endosomal et al., 1997; Odorizzi et al., 1998). membrane (Rue et al., 2008). Additionally, negative regulation of Human ESCRT-III consists of charged MVB protein (CHMP) Vps4 by Ist1 in the cytoplasm has also been proposed (Dimaano subunits, some of which have evolved multiple isoforms (see et al., 2008). In summary, ESCRT-III proteins form an insoluble Table 1). Studies in yeast indicate that these proteins are arranged lattice on the endosomal membrane via N-terminal interactions, into two subcomplexes, one that contains CHMP4A, CHMP4B or while their C-terminal domains act to recruit the AAA-ATPase CHMP4C (yeast Snf7; yeast nomenclature will hereafter be shown VPS4 and other regulatory proteins that are required for function. in parentheses unless otherwise indicated) and CHMP6 (Vps20), and another that consists of CHMP2A or CHMP2B (Vps2) and A membrane-deformation and -scission machinery CHMP3 (Vps24) (Babst et al., 2002). CHMP1A, CHMP1B (Vps46, The formation of ILVs within MVBs during cargo sorting requires Did2) and CHMP5 (Vps60) play important accessory and regulatory the coordinated deformation of the endosomal membrane to form roles in ESCRT function (Azmi et al., 2008; Lottridge et al., 2006; a nascent vesicle, followed by a membrane-scission event that Nickerson et al., 2006). The recently identified human protein releases the ILV into the MVB. The idea that ESCRT-III proteins CHMP7 (of which there is no known yeast homolog) interacts with were involved in membrane deformation was initially suggested CHMP4 proteins (Horii et al., 2006), although further investigations by the formation of filamentous polymers on the plasma are required to determine its function. membrane by overexpressed CHMP4A and CHMP4B: The CHMP proteins are similar in form to one another, each with surprisingly, the filaments formed circular arrays that were capable an N-terminal basic region and a C-terminal acidic region. Structural of deforming the membrane (Hanson et al., 2008). In agreement studies of CHMP3 suggest that CHMP proteins have an with these observations, Snf7 (human CHMP4) and Vps24 (human autoinhibitory activity whereby the uncomplexed protein folds into CHMP3) form helical polymers in vitro that can be disassembled a closed conformation through the attractive charges. However, by Vps4 in the presence of ATP. A role for Vps4 in the assembly following activation, the protein conformation may ‘open’, enabling of the ESCRT-III lattice is also suggested by the finding that, in CHMP proteins to associate with each other, forming a lattice on the the presence of ADP, Vps4 causes the chimeric filaments to bundle membrane (Lata et al., 2008a; Muziol et al., 2006; Shim et al., 2007; into extensive cables (Ghazi-Tabatabai et al., 2008). Recent work Zamborlini et al., 2006). It has been proposed that the N-terminal by Scott Emr and colleagues has also provided genetic and basic region associates with the membrane via electrostatic charges biochemical evidence that supports the idea that individual with the lipid bilayer (Muziol et al., 2006), although additional ESCRT-III subunits have specific functions and are recruited in anchorage may be provided by phosphoinositide-binding domains an ordered manner. Specifically, binding of Vps20 (human Journal of Cell Science ECSRTs in abscission and viral release 2169 CHMP6) to the membrane initiates the oligomerisation of Snf7 Vertical cross-section Horizontal cross-section subunits to form filaments at the MVBs. Subsequently, these filaments could encircle and concentrate endosomal cargo into defined regions of membrane. The oligomerisation reaction would then be terminated by the binding of the Vps24-Vps2 (human CHMP3-CHMP2) subcomplex, which also recruits Vps4 (Saksena et al., 2009; Teis et al., 2008). Plasma membrane A model has also been proposed for ESCRT disassembly: it has been suggested that individual subunits are ‘pumped’ through the central pore of the VPS4 complex into the cytoplasm (Scott et al., 2005a; Stuchell-Brereton et al., 2007; Yu et al., 2008). In line with the mechanism of function for spastin, another MIT-domain- containing AAA-ATPase (Roll-Mecak and Vale, 2008; White et al., 2007), the ESCRT-III subunits could be moved to binding sites within the central pore of the AAA-ATPase ring (Gonciarz et al., 2008; Shim et al., 2008), before being ‘pulled’ through via conformational changes induced during ATP binding and hydrolysis. It has been suggested that removing the subunits in this fashion could result in a constricting force that promotes vesicle extrusion and neck closure (Kieffer et al., 2008). A direct role for ESCRT-III in membrane scission has recently been demonstrated by reconstituting this activity using an in vitro Key system of MVB formation (Wollert et al., 2009a), and the ESCRT-III VPS4 subunit monomer VPS4 mechanistic details of this reaction have also started to be complex MIM MIT domain elucidated. Recent in vitro experiments conducted with bound to LIP5 Basic domain LIP5 dimer C-terminally truncated CHMP2A (CHMP2AΔCTD) and CHMP3 have demonstrated that these proteins can oligomerise and assemble into long tubular structures. Intriguingly, the Fig. 2. A model for ESCRT-III–VPS4-mediated membrane scission. Following coexpression of CHMP2AΔCTD, CHMP3 and VPS4 results in recruitment by upstream ESCRT complexes, ESCRT-III assembles on the the formation of tubular structures in which VPS4 is on the inside membrane. N-terminal basic domains (blue) of ESCRT-III subunits attach to of the tube, whereas the membrane-interaction sites of the CHMP the membrane, whereas the flexibly linked C-terminal MIMs (MIT-interaction motifs; red) project away from the membrane. The AAA-ATPase VPS4 proteins are on the outside. Importantly, the tubular arrays of assembles into a double-ring complex and interacts with ESCRT-III subunits ESCRT proteins had a diameter in the range of that seen for MVB- via N-terminal MIT (microtubule interaction and trafficking) domains vesicle and virus-particle stalks, suggesting that these tubular (yellow). The regulatory protein LIP5 (purple) forms a dimer and associates structures might be important for membrane scission. Interestingly, with the VPS4 complex (note that the MIT domains of LIP5 have been omitted for clarity). Narrowing of the membrane tube might be concurrent the addition of ATP caused the disassembly of the tubes (Lata with VPS4-mediated disassembly of the ESCRT-III lattice. It is possible that et al., 2008b). It is possible that extraction of ESCRT-III subunits subunit removal via mechanical extraction through the VPS4 complex could through a VPS4 ring could pull the membrane together, leading reduce the diameter of the tube and lead to constriction. Top two panels show to the resolution of the membrane stalk. Thus, in a similar way vertical and horizontal cross-sections of a wide membrane tube. The bottom that the enzyme dynamin forms a ring around inwardly budding two panels illustrate cross-sections of the thinner tube formed following the removal of the ESCRT-III lattice from the wider tube. vesicles, perhaps VPS4 – the only known energy-expending protein of the ESCRT pathway – acts on the internal membrane of an outwardly budding vesicle (Fig. 2). It should be noted that the tubular structures described by Lata et al. differ significantly discovery was preceded by the finding that the release of HIV-1 from the helical filaments reported by Ghazi-Tabatabai et al., although the reason for this difference is unclear (Lata particles could be blocked by the mutation of four amino acids TAP ) in the p6 protein of the HIV-1 Gag polyprotein (Gottlinger et al., 2008b; Ghazi-Tabatabai et al., 2008). One intriguing (P 7 10 possibility that might explain these conflicting results is that the et al., 1991; Huang et al., 1995). Mutation of the PTAP motif or two conformations might represent sequential stages of the truncation of the p6 protein resulted in fully formed viral particles ESCRT-III oligomeric structures that are required for sorting and that remained attached to the plasma membrane of the host cell by membrane-scission events. However, it is important to take into a membranous tether. Several other enveloped viruses from the account that these structures do not comprise all four ESCRT-III filovirus and rhabdovirus families also appear to contain short proteins, and recent evidence has shown that at least Snf7, peptide motifs that are essential for virus release at a late stage of Vps24 and Vps20 are required for MVB formation (Wollert et al., assembly and budding (Craven et al., 1999; Harty et al., 2000; Harty 2009a). et al., 1999). The term late domain (L-domain) was thus coined to describe these motifs. ESCRTs and virus-particle release The idea that viral L-domains were recruiting a host cell factor(s) ESCRTs and virus budding was supported by several findings. First, L-domains can function A short time after the ESCRT ‘budding’ machinery was initially in a positionally independent manner within viral Gag proteins discovered, a surprising new role for these proteins was defined in (Parent et al., 1995). Second, L-domains are interchangeable the release of enveloped retroviruses from the host cell. This between different viral Gag proteins (Parent et al., 1995; Yuan et al., Journal of Cell Science 2170 Journal of Cell Science 122 (13) Journal of Cell Science Table 1. Interactions between and requirement for ESCRT subunits in MVB biogenesis, viral-particle release and cytokinesis in mammalian cells Role in: MVB biogenesis Viral budding Cytokinesis Subunit* Known interaction partners ESCRT-0 3 4 HRS Tsg101, STAM, PtdIns(3)P, Required for EGFR and EGF Not required Recruited to midbody 1,2 ubiquitin, SNAP25, VPS37A, degradation clathrin, Cep55 STAM1 and STAM2 HRS, UBPY, ubiquitin, AMSH Required for EGFR degradation N.D. N.D. ESCRT-I Tsg101 (Vps23) All ESCRT-I subunits, EAP30, Recruited by HRS to endosomal Recruited to plasma membrane by Recruited to midbody by Cep55 to 12,13 EAP45, ALIX, HRS, Bcr, TOM1, membrane; required for EGFR and HIV-1 Gag to mediate virus mediate abscission 2,6-9 10,11 TOM1L1, TOM1L2, ubiquitin, EGF degradation budding Cep55, Rock1, IQGAP, CD2AP, HD-PTP 14-16 12 VPS28-I and VPS28-II Tsg101, CHMP6, Bcr, ESCRT-II Blocking antibody inhibits EGF Required Required degradation VPS37A, B, C, D Tsg101, Cep55; VPS37A binds to VPS37A required for EGFR VPS37B and VPS37C required for N.D. 17 16,18 HRS degradation HIV-1 release MVB12A, MVB12B Tsg101; MVB12A binds to VPS37B Recruited to aberrant endosomes Role in maturation and/or infectivity N.D. of HIV-1 ESCRT-II EAP30, EAP20, EAP45 CHMP6, VPS28-I, ubiquitin, Tsg101, May be required for EGFR Not required N.D. with one another degradation; not required for 20,21 MHC-1 degradation ESCRT-III CHMP1A and CHMP1B (Did2) – MITD1, UBPY, LIP5, AMSH, hIST1, GFP fusion causes aberrant Overexpressed YFP fusion inhibits Required for abscission 22 23 contain MIM VPS4, with one another; endosomes budding CHIMP1B binds to CHMP2A, CHMP4B, CHMP5, spastin CHMP2A and CHMP2B (Vps2) – CHMP2A binds to AMSH, MITD1, Expression of truncated form causes CHMP2A-YFP fusion inhibits CHMP2A recruited to midbody contain MIM VPS4, CHMP1B, CHMP3, aberrant endosomes budding; CHMP2B has no DN 26,27 CHMP4A, CHMP4B, CHMP5; effect CHMP2B binds to CHMP3 CHMP3 (Vps24) CHMP2A, CHMP2B, CHMP4B, Required for proper EGFR Overexpressed YFP fusion inhibits Abscission inhibited by DN 28 26 VPS4, AMSH degradation budding mutant 30,13 CHMP4A, B, C (Snf7) – CHMP6, ALIX, Brox, HD-PTP, Expression of a truncated form YFP fusion proteins inhibit Required for abscission 25 26,27,30 contain MIM2 VPS4, with one another; causes aberrant endosomes budding CHMP4B binds to CHMP1B, CHMP3, CHMP5, CHMP7; CHMP4C binds to AMSH, UBPY CHMP5 (Vps60) CHMP1B, CHMP2A, CHMP4A, Required for proper EGFR and YFP fusion was shown to inhibit, but Recruited to midbody 31,32 CHMP4B, LIP5 TGF R degradation depletion enhanced, virus 27,31 release CHMP6 (Vps20) – contains MIM2 CHMP4A, CHMP4B, EAP45, Required for proper EGFR Not required N.D. EAP20, EAP30, VPS28-I, VPS4 degradation CHMP7 CHMP4B GFP fusion inhibits EGFR GFP fusion inhibits VLP release N.D. degradation ESCRT-associated proteins ALIX Tsg101, endophilin, CHMP4A, Not essential for EGFR Required for EIAV budding; minor Recruited by Cep55 to midbody to 34,35 36,27 12,13 CHMP4B, CHMP4C, Cep55, degradation activity in HIV-1 release mediate abscission CD2AP, Cin85 Table 1 continued on next page. ECSRTs in abscission and viral release 2171 2000) and hence are not virus specific. Additionally, a number of studies have also implicated an aspect of the ubiquitylation machinery in viral budding: proteasome inhibitors were shown to cause an L-domain-defective phenotype in cells infected with HIV-1 or Rous sarcoma virus, or that were expressing Simian ) Gag (Patnaik et al., 2000; immunodeficiency virus type (SIV mac Schubert et al., 2000; Strack et al., 2000). In 2001, the search for the HIV-1 ‘budding factor’ ended when the interaction between the PTAP motif of HIV-1 p6 and the ESCRT-I protein Tsg101 was shown, with the demonstration that Tsg101 recruits the entire ESCRT machinery to mediate virus budding (Demirov et al., 2002; Garrus et al., 2001; Martin-Serrano et al., 2001; VerPlank et al., 2001). This finding sparked a flood of interest in the field and, since then, several other viruses, including those from the arenavirus and paramyxovirus families, have also been found to contain L-domains (Bieniasz, 2006; Perez et al., 2003; Schmitt et al., 2005). Interestingly, the requirement of a functional ESCRT pathway for particle release is not restricted to RNA viruses. Recent work has demonstrated that the enveloped DNA viruses hepatitis B and herpes simplex virus type 1 also require the ESCRT machinery, because the expression of dominant-negative forms of CHMP3, CHMP4B and CHMP4C or of catalytically inactive VPS4 proteins inhibits virus release (Crump et al., 2007; Lambert et al., 2007; Watanabe et al., 2007). Although PTAP (and PSAP) L-domains recruit the ESCRT machinery via Tsg101, other L-domains access the complexes L L-domains bind the adaptor through different means. LYPx protein ALIX, which in turn binds and recruits the ESCRT machinery via the CHMP4 proteins (Fisher et al., 2007; Martin- Serrano et al., 2003b; McCullough et al., 2008; Strack et al., 2003; Usami et al., 2007; von Schwedler et al., 2003; Zhai et al., 2008). The PPxY motif enlists members of the NEDD4 family of ubiquitin ligases through interactions with WW domains (Bouamr et al., 2003; Garnier et al., 1996; Harty et al., 2000; Harty et al., 1999; Kikonyogo et al., 2001; Martin-Serrano et al., 2005; Yasuda et al., 2002), although the precise link between the NEDD4-like proteins and the ESCRT machinery is still unknown (Martin-Serrano, 2007). Finally, a fourth L-domain encoded by the FPIV amino acid motif has been identified in the matrix protein of the paramyxovirus simian virus 5, although the mechanism of ESCRT recruitment by this L-domain is currently unknown (Schmitt et al., 2005). Interestingly, many of the viruses studied contain more than one type of L-domain motif (Bouamr et al., 2003; Gottwein et al., 2003; Segura-Morales et al., 2005). For example, HIV-1 contains binding sites for Tsg101 and ALIX (Strack et al., 2003), and, although it lacks a PPxY motif, the surprising influence of NEDD4L (also known as Nedd4-2s) ubiquitin-ligase activity on HIV-1 budding has recently been shown (Chung et al., 2008; Usami et al., 2008). An additional ALIX-binding site has also been identified in the nucleocapsid protein of HIV-1 Gag; this site might play an auxiliary role in virus release (Popov et al., 2008). It is well established that the interaction between the PTAP L-domain motif and Tsg101 is the preferential means of HIV-1 release in HEK293T cells; however, mutation of the PTAP motif renders the virus reliant on its LYPx motif (Fisher et al., 2007; Usami et al., 2007), and, independently, on a region in the C-terminal domain of capsid (CP) and the SP1 region of the Gag polyprotein, for NEDD4L activity (Chung et al., 2008; Usami et al., 2008). The evolution of ‘back-up’ L-domains illustrates the crucial role of ESCRT proteins and ESCRT-associated cofactors in viral release. However, it is not completely clear why viruses have evolved multiple L-domains. One possibility could be Journal of Cell Science Table 1. Continued Role in: MVB biogenesis Viral budding Cytokinesis Subunit* Known interaction partners ESCRT-associated proteins 31 24,40 LIP5 – CHMP1A, CHMP1B, CHMP5, Required for proper EGFR Required for HIV-1 release Binding partners are required contains MIT domains VPS4, hIST1 degradation 11,26 13 VPS4A, VPS4B – CHMP1A, CHMP1B, CHMP2A, Required for dissociation of Required for viral budding Abscission inhibited by DN mutant contain MIT domain CHMP2B, CHMP3, CHMP4A, complexes from endosomal CHMP4B, CHMP4C, LIP5, hIST1 membrane AMSH – CHMP1A, CHMP1B, CHMP2A, Depletion increases rate of EGFR Not essential Recruited to midbody; depletion causes 38 4 contains MIT domain CHMP3, CHMP4C, STAM, hIST1 degradation moderate defect UBPY – CHMP1A, CHMP1B, CHMP4C, Required for deubiquitylation of N.D. Catalytic mutant inhibits abscission; 39 4 contains MIT domain STAM, hIST1 EGFR recruited to midbody 40 24,40 24,26 hIST1 – CHMP1A, CHMP1B, MITD1, Not required for EGFR degradation Not essential Required for abscission spastin, VPS4, LIP5, AMSH, contains MIM1 and MIM2 UBPY *Yeast nomenclature is shown in parentheses. Abbreviations not included in main text: DN, dominant-negative; EGFR, epidermal growth factor receptor; EIAV, equine infectious anaemia virus; GFP, green fluorescent protein; N.D. not determined; PtdIns(3)P, phosphatidylinositol 3-phosphate; TGF R, transforming growth factor- receptor; VLP, virus-like particle; YFP, yellow fluorescent protein. 1 2 3 4 5 6 7 8 9 (Urbe et al., 2003); (Raiborg et al., 2008); (Pornillos et al., 2003); (Mukai et al., 2008); (Kanazawa et al., 2003); (Bache et al., 2003); (Katzmann et al., 2003); (Bishop et al., 2002); (Babst et al., 10 11 12 13 14 15 16 2000); (Martin-Serrano et al., 2001); (Garrus et al., 2001); (Carlton and Martin-Serrano, 2007); (Morita et al., 2007b); (Martin-Serrano et al., 2003a); (Tanzi et al., 2003); (Stuchell et al., 2004); 17 18 19 20 21 22 23 24 (Bache et al., 2004); (Eastman et al., 2005); (Morita et al., 2007a); (Langelier et al., 2006); (Bowers et al., 2006); (Howard et al., 2001); (Agromayor and Martin-Serrano, 2006); (Bajorek et al., 25 26 27 28 29 30 31 32 2009); (Shim et al., 2007); (von Schwedler et al., 2003); (Martin-Serrano et al., 2003b); (Bache et al., 2006); (Dukes et al., 2008); (Carlton et al., 2008); (Ward et al., 2005); (Shim et al., 2006); 33 34 35 36 37 38 39 40 (Horii et al., 2006); (Schmidt et al., 2004); (Cabezas et al., 2005); (Strack et al., 2003); (Babst et al., 1998); (McCullough et al., 2004); (Row et al., 2007); (Agromayor et al., 2009). 2172 Journal of Cell Science 122 (13) that differing expression levels of host cofactors require alternative actomyosin ring contracts, the resulting indentation around the cell ESCRT entry routes in different cells types. Alternatively, because is termed the cleavage furrow. Ingression of the furrow ultimately viral proteins are in competition with other cellular factors for leads to constriction of the plasma membrane around the spindle ESCRT adaptor proteins (Pornillos et al., 2003), it is perhaps microtubules and the formation of a condensed midbody structure advantageous for the viral Gag protein to interact with as many between mother and daughter cell. ESCRT recruiters as possible. Following the massive plasma-membrane remodelling gymnastics involved in cleavage-furrow ingression, the final hurdle Other ESCRT functions, in addition to membrane scission before liberation of the daughter cells is the severing of the Unlike MVB biogenesis, it is commonly thought that plasma- membranous tether that joins them. This process, known as membrane deformation during retroviral assembly is aided by the abscission, requires the coordinated actions of many proteins that concentrated oligomerisation of viral Gag proteins at the membrane. are involved in membrane trafficking, vesicle targeting and vesicle Moreover, the L-domain-defective phenotype suggests that ESCRT fusion (Fig. 3). Abscission is preceded by the formation of a proteins are only required to mediate scission in the final release centriolin-enriched, γ-tubulin-containing ‘midbody ring’ structure step of viral budding, although an additional early function of the (Gromley et al., 2003; Gromley et al., 2005), to which vesicle- ESCRT machinery in HIV-1 budding has been recently proposed targeting proteins of the exocyst complex are recruited. The exocyst (Carlson et al., 2008). However, in addition to the classic late- is a large multi-subunit protein complex that functions in the budding defects, the mutation of L-domains in some retroviruses, tethering of Golgi-derived secretory vesicles to distinct plasma- or the depletion or disruption of some ESCRT proteins, can lead membrane regions, and its localisation to the midbody ring seems to other problems, ranging from early assembly blocks to maturation to be required for cytokinesis (Gromley et al., 2005). Subsequent failure. Observations of cells infected with PPPY L-domain mutants recruitment to the midbody of endobrevin (a v-SNARE protein; of human T-cell leukaemia virus type 1 and Mason-Pfizer monkey also known as VAMP8) and syntaxin-2 (a t-SNARE protein) by virus by electron microscopy revealed an early-budding phenotype; components of the midbody ring facilitates membrane-fusion events Gag protein accumulated underneath the plasma membrane, but little that are crucial for abscission (Gromley et al., 2005; Low et al., or no assembled virus particles were found attached to the cell 2003). Moreover, important regulators of the SNAREs, such as the surface by membranous tethers (Bouamr et al., 2003; Gottwein et al., Rab family of GTPases, have also been implicated in the terminal 2003; Le Blanc et al., 2002). A different phenotype was seen on stages of cytokinesis. Specifically, endocytic Rab proteins (Rab35, deletion of the p12 L-domain-containing protein or PPPY motif of Rab11 and, in certain cells, Rab8) are also key regulators of vesicle murine leukaemia virus; in this viral context, morphologically traffic during the final stages of cell division (Fielding et al., 2005; tubular virions were observed, as well as viral particles that were Kouranti et al., 2006; Pohl and Jentsch, 2008; Wilson et al., 2005; attached to each other in chains (Yuan et al., 2000). A similar Yu et al., 2007). In addition, the Rab11-family-interacting proteins phenomenon also occurred on overexpression of a dominant- FIP3 and FIP4 are thought to play key roles in cytokinesis through negative CHMP2A construct (Martin-Serrano et al., 2003b). the transport of Rab11-positive vesicles from recycling endosomes Additionally, recent work with the newly identified ESCRT-I to the cleavage furrow and the midbody (Fielding et al., 2005; proteins MVB12A and MVB12B showed that these proteins have Prekeris and Gould, 2008; Wilson et al., 2005). a function in viral infectivity, but not in virus budding. The ESCRT localisation at the midbody depletion of MVB12A or MVB12B resulted in the accumulation Previous models of cytokinesis proposed that the resolution of the of amorphous, aberrant viral particles, although particle release was not inhibited. However, the overexpression of these proteins did membranous tether between two cells could be achieved by reduce viral budding, and this was dependent on the ability of the membrane-fusion events that are mediated by SNAREs. According proteins to bind Tsg101 and on their phosphorylation (Morita et al., to these models, the combination of membrane addition by vesicle 2007a). Altogether, these observations suggest that, in addition to fusion to the plasma membrane, and the influx and fusion of a function in membrane scission, some viruses might also require endocytic and secretory vesicles to the midbody region (effectively additional aspects of the ESCRT machinery for assembly and/or making ‘holes’ in the tether) was thought to be sufficient to mediate maturation. membrane scission (Gromley et al., 2005). A key activity in this model is the homotypic fusion of vesicles at the midbody in order ESCRTs and daughter-cell release to facilitate the final event in abscission. However, experimental Cytokinesis, the process of cytoplasmic division, is the final stage of evidence supporting homotypic fusion during abscission has been the cell cycle following mitosis. It is at this final stage that one cell elusive. Crucially, the topology of the membrane-scission event that becomes two. Remarkably, it now seems that the ESCRT machinery is required for abscission is identical to the topology of the is required for a terminal step in this process. In animal cells, the act membrane-scission events that are known to be facilitated by the of cytokinesis is driven by the strictly regulated contraction of an ESCRT machinery – MVB formation and retroviral budding actomyosin ring around the equator of the cell. The position of the (Fig. 1). This analogy and the functional parallels between these contractile ring and the initiation of contraction are determined by ESCRT-mediated processes have shed light on the cellular signals from the mitotic-spindle microtubules at the spindle midzone mechanisms that facilitate abscission. (the region of microtubule overlap), and might also be influenced by In the same way that many enveloped viruses recruit the ESCRT signals from the aster microtubules at the poles of the cell (Barr and machinery to mediate scission of the membranous tether between Gruneberg, 2007; Bringmann and Hyman, 2005; Eggert et al., 2006; virion and host cell, Tsg101 and ALIX are recruited to the midbody Glotzer, 2005). The accumulation of actin and myosin-II filaments, to mediate the release of daughter cell from mother cell (Carlton together with numerous regulatory proteins, occurs at right angles to and Martin-Serrano, 2007; Morita et al., 2007b). Cep55 (centrosome the spindle midzone, which ensures the equal distribution of genetic protein 55kDa), a midbody component that is crucial for abscission material, organelles and cytoplasm to each progeny cell. When the (Fabbro et al., 2005; Martinez-Garay et al., 2006; Zhao et al., 2006), Journal of Cell Science ECSRTs in abscission and viral release 2173 binds to both Tsg101 and ALIX, and the disruption of this by experiments in which cells were engineered to express ALIX interaction results in cytokinesis failure. It is important to note that mutants that cannot bind to ESCRT-III. In these cells, aberrant the interaction of Tsg101 and ALIX with Cep55 is not required for midbodies formed, in which tubulin staining was visible across the viral budding (Carlton and Martin-Serrano, 2007; Morita et al., central region of interdigitating microtubules. This is in contrast to 2007b), suggesting that Cep55 and viral Gag proteins play cells expressing wild-type ALIX, in which a dense accumulation functionally equivalent roles in recruiting the ESCRT machinery of protein (presumably ESCRT-III) prevented complete tubulin to facilitate topologically equivalent membrane-scission events at staining and a characteristic gap at the midbody was observed different cellular locations. (Carlton et al., 2008). In summary, these observations suggest an Importantly, it is probable that other components of the ESCRT organised spatial and temporal recruitment of ESCRT proteins to machinery are also required for abscission, because the interaction the midbody during cytokinesis. of Tsg101 with VPS28 (a component of ESCRT-I) is also required Initial mapping studies showed that Cep55 binds to a conserved for the completion of cytokinesis (Carlton and Martin-Serrano, peptide at the proline-rich region (PRR) of ALIX (Carlton et al., 2007), and interactions between Tsg101 and other proteins that are 2008; Morita et al., 2007b). However, the Cep55-binding peptide involved in cytokinesis – in particular CD2AP, ROCK1 and IQGAP in ALIX is not found in Drosophila, suggesting that different – have also been shown (Morita et al., 2007b). The involvement mechanisms to recruit the ESCRT machinery during abscission of the core ESCRT machinery in cytokinesis was initially suggested might exist in other organisms. Biochemical data also indicate by the dominant-negative effect observed when catalytically inactive that Tsg101 and ALIX compete for binding to the ESCRT- and VPS4 or ESCRT-III subunits were overexpressed (Carlton and ALIX-binding region (EABR) of Cep55, and the crystal structure Martin-Serrano, 2007; Dukes et al., 2008; Morita et al., 2007b). of the ALIX-Cep55 complex shows that the EABR forms a Importantly, direct evidence for ESCRT-III function in abscission dimeric noncanonical coiled coil that cannot simultaneously bind is provided by the finding that the ESCRT-III-binding site in ALIX to Tsg101. On the basis of these observations, a model has been has an essential role in this process (Carlton et al., 2008; Morita proposed in which multiple Cep55 dimers are required for et al., 2007b). ESCRT recruitment to the midbody (Lee et al., 2008; Wollert In terms of localisation, confocal-microscopy studies with et al., 2009b). immunostaining have uncovered an interesting pattern. On one hand, ESCRT function at the midbody exogenously expressed CHMP2A, CHMP4A, CHMP5, hIST1 and Although the ESCRT proteins appear to be recruited for membrane- endogenous VPS4 were found at distinct rings on both sides of the midbody structure (Agromayor et al., 2009; Bajorek et al., 2009; scission events, it is formally possible that, rather than having a Morita et al., 2007b). By contrast, fluorescently tagged forms of direct role in cytokinesis, an endosomal sorting function could be ALIX and Tsg101 were found at the central region of the midbody the required activity for abscission (Prekeris and Gould, 2008). (Carlton and Martin-Serrano, 2007), suggesting that different However, this view is countered by recent discoveries in Archaea, components of the ESCRT machinery might localise at which is a separate domain of life that lacks endomembrane different regions of the midbody. However, it is known that protein structures and is separated from humans by two-billion years of density at the central region of the midbody masks epitopes, and evolution. Remarkably, homologues of ESCRT-III proteins and therefore a gap in this region determined by immunostaining should VPS4 have been identified in Sulfolobus, a member of the Kingdom be interpreted with caution. Evidence that ESCRT proteins constitute Crenarchaea (Hobel et al., 2008; Obita et al., 2007). Functional a major component of the midbody structure has also been suggested experiments have demonstrated that cell-cycle regulation and mid- Endosome- or Golgi-derived Microtubules vesicles ROCK1 IQGAP1 Cep55 CD2AP Tsg101 ALIX VPS4 hIST1-CHMP1B Spastin SNAREs Exocyst ESCRTs Syntaxin-2 Rab GTPases Spastin Endobrevin Fig. 3. A model for ESCRT-mediated abscission. Golgi- and endosome-derived vesicles are transported to the midbody along microtubules, a process that is regulated by Rab GTPases. Association with the exocyst-tethering complex at the midbody may constrain the site of vesicle fusion. The v-SNARE endobrevin (also known as VAMP8) and the plasma-membrane-associated t-SNARE syntaxin-2 mediate vesicle fusion with the plasma membrane. Cep55 recruits ALIX and Tsg101 to the midbody for subsequent ESCRT-III assembly. Tsg101 can interact with other proteins that are involved in cytokinesis – in particular CD2AP, ROCK1 and IQGAP. The coordinated recruitment of VPS4 and spastin, along with other regulatory proteins (hIST1 and CHMP1B), to the midbody may complete abscission by severing microtubules and mediating membrane fusion of the remaining tether via ESCRT-III disassembly (arrows). ESCRT-III Journal of Cell Science Midbody 2174 Journal of Cell Science 122 (13) cell localisation of these proteins occurs during cell division, and emerging picture is one in which alternative adaptor proteins (such the expression of Vps4 mutants also caused phenotypes indicative as Hrs, viral proteins and Cep55) recruit the core ESCRT machinery of cell-division failure (Lindas et al., 2008; Samson et al., 2008). to resolve different membranous tethers by facilitating topologically These data suggest that, in fact, the involvement of ESCRTs in cell equivalent membrane-scission events. In spite of recent progress division represents an ancestral role for these proteins, and the in this area, the most pressing question of how exactly membrane endosomal sorting function of ESCRTs in mammalian cells has scission is achieved is still unanswered. At present, we do not know evolved subsequently. This supports the hypothesis that ESCRT whether the ESCRT proteins themselves mediate this membrane- proteins play an essential role in abscission, which is independent scission event, or whether their role is to recruit additional proteins of endosomal sorting. This idea is also supported by the phenotypes to do the job. observed in hIST1-depleted cells, which are defective for abscission, An additional layer of complexity in the ESCRT machinery that although other ESCRT functions (such as the sorting of EGFR to is poorly understood is the gene expansion in humans compared MVBs and HIV-1 budding) are unaltered (Agromayor et al., 2009; with yeast. For example, there are three isoforms of CHMP4 and Bajorek et al., 2009). two isoforms of VPS4 in humans, whereas yeast only have one Midbody abscission by the ESCRT machinery presents a problem form of each protein. More strikingly, the combination of one form that needs to be resolved in terms of the diameter of the tether: the of Tsg101, four isoforms of VPS37 (A, B, C and D), two of VPS28 membranous tethers that restrain MVB vesicles and viral particles (I and II) and two of MVB12 (A and B), gives a possible 16 are thought to have a diameter in the region of 50-100 nm, whereas different ESCRT-I complexes in humans. Thus, it will be important the midbody ring structure between two daughter cells is to determine whether different subsets of ESCRT proteins are significantly larger, at around 1.5-2.0 μm (Gromley et al., 2005). preferentially required during endosomal sorting, retroviral However, there are several models that could explain the ‘thinning’ replication and cytokinesis. Preliminary evidence that supports this of the midbody to a point at which the ESCRT machinery could idea includes functional studies that compared the different act directly. One possibility is that ESCRT proteins play a direct isoforms of CHMP4; these show that the overexpression role in midbody thinning, as it has been suggested that membrane of YFP-CHMP4C preferentially inhibits cytokinesis, whereas expulsion via budding vesicles may also be required to resolve the YFP-CHMP4B is the most potent inhibitor of HIV-1 release tether (Dubreuil et al., 2007). Alternatively, the fusion of secretory (Carlton et al., 2008). These results suggest that different isoforms vesicles with the plasma membrane might give rise to a tether within of ESCRT-III might have evolved to mediate different scission the midbody on which the ESCRT machinery could act (Fig. 3). events. However, more work is needed to confirm this hypothesis Interestingly, a role for spastin, a microtubule-severing enzyme, has and to fully understand the functional differences within this and also recently been implicated in ESCRT-mediated membrane other genes that have been expanded in the human ESCRT scission. Spastin (60-kDa isoform) interacts with the ESCRT-III machinery. It will also be interesting to determine the regulation protein CHMP1B (Reid et al., 2005) and localises to the midbody and function of these multiple isoforms and to investigate the in an MIT-domain- and CHMP1B-dependent manner. Depletion of constellation of poorly characterised proteins that bind to spastin by siRNA, or the expression of CHMP1B non-binding ESCRT-III. mutants, causes cytokinetic failures, consistent with a role in In conclusion, it is clear that, in addition to its role in viral abscission (Connell et al., 2009; Yang et al., 2008). One protein infection, the ESCRT machinery is involved in several other that could help coordinate the mechanical activities of VPS4 with cellular processes. Because malfunctions of these proteins have been those of spastin is hIst1, which binds to both ATPases (Agromayor implicated in diverse disease pathologies, developments in the et al., 2009). Both hIst1 and CHMP1 proteins are required to recruit understanding of ESCRT function could therefore provide important VPS4 to the midbody (Bajorek et al., 2009). This phenotype could clues about the mechanisms of disease and lead to future therapeutic be explained by a mechanism in which the CHMP1B-hIst1 complex interventions. creates a network of MIMs that would increase the avidity for VPS4 Research in Juan Martin-Serrano’s laboratory is funded by the and LIP5 at the midbody. Both CHMP1B and hIst1 also bind Medical Research Council UK, the Lister Institute of Preventive additional MIT-domain-containing proteins that might be required Medicine and the EMBO Young Investigator Programme. Deposited for abscission, including two deubiquitylating enzymes, AMSH and in PMC for release after 6 months. UBPY, and other proteins of unknown function (Agromayor et al., 2009). In fact, a role for UBPY and AMSH has been suggested References (Mukai et al., 2008; Pohl and Jentsch, 2008), but more work is needed Agromayor, M. and Martin-Serrano, J. (2006). Interaction of AMSH with ESCRT-III and deubiquitination of endosomal cargo. J. Biol. Chem. 281, 23083-23091. to determine whether the recruitment of these deubiquitylating Agromayor, M., Carlton, J. G., Phelan, J. P., Matthews, D. R., Carlin, L. M., Ameer- enzymes by the ESCRT machinery is required for abscission. Beg, S., Bowers, K. and Martin-Serrano, J. (2009). Essential Role of hIST1 in In summary, the archaean ancestry and the association of ESCRT Cytokinesis. Mol. Biol. Cell 20, 1374-1387. Azmi, I., Davies, B., Dimaano, C., Payne, J., Eckert, D., Babst, M. and Katzmann, D. proteins with additional regulatory and enzymatic proteins suggests J. (2006). Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a conserved that the ESCRT machinery has a role in membrane scission, rather VSL region in Vta1. J. Cell Biol. 172, 705-717. than an endosomal sorting function, at the midbody during Azmi, I. F., Davies, B. A., Xiao, J., Babst, M., Xu, Z. and Katzmann, D. J. (2008). ESCRT-III family members stimulate Vps4 ATPase activity directly or via Vta1. Dev. cytokinesis. It is becoming clearer that the coordination of different Cell 14, 50-61. activities such as microtubule severing, deubiquitylation and Babst, M., Sato, T. K., Banta, L. M. and Emr, S. D. (1997). Endosomal transport function in yeast requires a novel AAA-type ATPase, Vps4p. EMBO J. 16, 1820- mechanical energy expenditure, with ESCRT function, is required to achieve abscission. Babst, M., Wendland, B., Estepa, E. J. and Emr, S. D. (1998). The Vps4p AAA ATPase regulates membrane association of a Vps protein complex required for normal endosome function. EMBO J. 17, 2982-2993. Concluding remarks and outstanding questions Babst, M., Odorizzi, G., Estepa, E. J. and Emr, S. D. (2000). Mammalian tumor Although we have made significant progress in recent years towards susceptibility gene 101 (TSG101) and the yeast homologue, Vps23p, both function in understanding ESCRT function, many questions remain. The late endosomal trafficking. Traffic 1, 248-258. Journal of Cell Science ECSRTs in abscission and viral release 2175 Babst, M., Katzmann, D. J., Estepa-Sabal, E. J., Meerloo, T. and Emr, S. D. (2002). Fielding, A. B., Schonteich, E., Matheson, J., Wilson, G., Yu, X., Hickson, G. R., Escrt-III: an endosome-associated heterooligomeric protein complex required for mvb Srivastava, S., Baldwin, S. A., Prekeris, R. and Gould, G. W. (2005). Rab11-FIP3 sorting. Dev. Cell 3, 271-282. and FIP4 interact with Arf6 and the exocyst to control membrane traffic in cytokinesis. Bache, K. G., Brech, A., Mehlum, A. and Stenmark, H. (2003). Hrs regulates EMBO J. 24, 3389-3399. multivesicular body formation via ESCRT recruitment to endosomes. J. Cell Biol. 162, Fisher, R. D., Chung, H. Y., Zhai, Q., Robinson, H., Sundquist, W. I. and Hill, C. P. 435-442. (2007). Structural and biochemical studies of ALIX/AIP1 and its role in retrovirus Bache, K. G., Slagsvold, T., Cabezas, A., Rosendal, K. R., Raiborg, C. and Stenmark, budding. Cell 128, 841-852. H. (2004). The growth-regulatory protein HCRP1/hVps37A is a subunit of mammalian Garnier, L., Wills, J. W., Verderame, M. F. and Sudol, M. (1996). WW domains and ESCRT-I and mediates receptor down-regulation. Mol. Biol. Cell 15, 4337-4346. retrovirus budding. Nature 381, 744-745. Bache, K. G., Stuffers, S., Malerod, L., Slagsvold, T., Raiborg, C., Lechardeur, D., Garrus, J. E., von Schwedler, U. K., Pornillos, O. W., Morham, S. G., Zavitz, K. H., Walchli, S., Lukacs, G. L., Brech, A. and Stenmark, H. (2006). The ESCRT-III subunit Wang, H. E., Wettstein, D. A., Stray, K. M., Cote, M., Rich, R. L. et al. (2001). hVps24 is required for degradation but not silencing of the epidermal growth factor Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding. Cell receptor. Mol. Biol. Cell 17, 2513-2523. 107, 55-65. Bajorek, M., Morita, E., Skalicky, J. J., Morham, S. G., Babst, M. and Sundquist, W. Ghazi-Tabatabai, S., Saksena, S., Short, J. M., Pobbati, A. V., Veprintsev, D. B., I. (2009). Biochemical analyses of human IST1 and its function in cytokinesis. Mol. Crowther, R. A., Emr, S. D., Egelman, E. H. and Williams, R. L. (2008). Structure Biol. Cell 20, 1360-1373. and disassembly of filaments formed by the ESCRT-III subunit Vps24. Structure 16, Barr, F. A. and Gruneberg, U. (2007). Cytokinesis: placing and making the final cut. Cell 1345-1356. 131, 847-860. Gill, D. J., Teo, H., Sun, J., Perisic, O., Veprintsev, D. B., Emr, S. D. and Williams, R. Bieniasz, P. D. (2006). Late budding domains and host proteins in enveloped virus release. L. (2007a). Structural insight into the ESCRT-I/-II link and its role in MVB trafficking. Virology 344, 55-63. EMBO J. 26, 600-612. Bishop, N. and Woodman, P. (2000). ATPase-defective mammalian VPS4 localizes to Gill, D. J., Teo, H., Sun, J., Perisic, O., Veprintsev, D. B., Vallis, Y., Emr, S. D. and aberrant endosomes and impairs cholesterol trafficking. Mol. Biol. Cell 11, 227-239. Williams, R. L. (2007b). Structural studies of phosphoinositide 3-kinase-dependent traffic Bishop, N., Horman, A. and Woodman, P. (2002). Mammalian class E vps proteins to multivesicular bodies. Biochem. Soc. Symp. 74, 47-57. recognize ubiquitin and act in the removal of endosomal protein-ubiquitin conjugates. Glotzer, M. (2005). The molecular requirements for cytokinesis. Science 307, 1735-1739. J. Cell Biol. 157, 91-101. Gonciarz, M. D., Whitby, F. G., Eckert, D. M., Kieffer, C., Heroux, A., Sundquist, W. Bouamr, F., Melillo, J. A., Wang, M. Q., Nagashima, K., de Los Santos, M., Rein, A. I. and Hill, C. P. (2008). Biochemical and structural studies of yeast Vps4 and Goff, S. P. (2003). PPPYVEPTAP motif is the late domain of human T-cell leukemia oligomerization. J. Mol. Biol. 384, 878-895. virus type 1 Gag and mediates its functional interaction with cellular proteins Nedd4 Gottlinger, H. G. (2001). The HIV-1 assembly machine. AIDS 15 Suppl. 5, S13-S20. and Tsg101 [corrected]. J. Virol. 77, 11882-11895. Gottlinger, H. G., Dorfman, T., Sodroski, J. G. and Haseltine, W. A. (1991). Effect of Bowers, K., Lottridge, J., Helliwell, S. B., Goldthwaite, L. M., Luzio, J. P. and Stevens, mutations affecting the p6 gag protein on human immunodeficiency virus particle release. T. H. (2004). Protein-protein interactions of ESCRT complexes in the yeast Proc. Natl. Acad. Sci. USA 88, 3195-3199. Saccharomyces cerevisiae. Traffic 5, 194-210. Gottwein, E., Bodem, J., Muller, B., Schmechel, A., Zentgraf, H. and Krausslich, H. Bowers, K., Piper, S. C., Edeling, M. A., Gray, S. R., Owen, D. J., Lehner, P. J. and G. (2003). The Mason-Pfizer monkey virus PPPY and PSAP motifs both contribute to Luzio, J. P. (2006). Degradation of endocytosed epidermal growth factor and virally virus release. J. Virol. 77, 9474-9485. ubiquitinated major histocompatibility complex class I is independent of mammalian Gromley, A., Jurczyk, A., Sillibourne, J., Halilovic, E., Mogensen, M., Groisman, I., ESCRTII. J. Biol. Chem. 281, 5094-5105. Blomberg, M. and Doxsey, S. (2003). A novel human protein of the maternal centriole Bringmann, H. and Hyman, A. A. (2005). A cytokinesis furrow is positioned by two is required for the final stages of cytokinesis and entry into S phase. J. Cell Biol. 161, consecutive signals. Nature 436, 731-734. 535-545. Burd, C. G. and Emr, S. D. (1998). Phosphatidylinositol(3)-phosphate signaling mediated Gromley, A., Yeaman, C., Rosa, J., Redick, S., Chen, C. T., Mirabelle, S., Guha, M., by specific binding to RING FYVE domains. Mol. Cell 2, 157-162. Sillibourne, J. and Doxsey, S. J. (2005). Centriolin anchoring of exocyst and SNARE Cabezas, A., Bache, K. G., Brech, A. and Stenmark, H. (2005). Alix regulates cortical complexes at the midbody is required for secretory-vesicle-mediated abscission. Cell actin and the spatial distribution of endosomes. J. Cell Sci. 118, 2625-2635. 123, 75-87. Carlson, L. A., Briggs, J. A., Glass, B., Riches, J. D., Simon, M. N., Johnson, M. C., Hanson, P. I., Roth, R., Lin, Y. and Heuser, J. E. (2008). Plasma membrane deformation Muller, B., Grunewald, K. and Krausslich, H. G. (2008). Three-dimensional analysis by circular arrays of ESCRT-III protein filaments. J. Cell Biol. 180, 389-402. of budding sites and released virus suggests a revised model for HIV-1 morphogenesis. Hartmann, C., Chami, M., Zachariae, U., de Groot, B. L., Engel, A. and Grutter, M. Cell Host Microbe 4, 592-599. G. (2008). Vacuolar protein sorting: two different functional states of the AAA-ATPase Carlton, J. G. and Martin-Serrano, J. (2007). Parallels between cytokinesis and retroviral Vps4p. J. Mol. Biol. 377, 352-363. budding: a role for the ESCRT machinery. Science 316, 1908-1912. Harty, R. N., Paragas, J., Sudol, M. and Palese, P. (1999). A proline-rich motif within Carlton, J. G., Agromayor, M. and Martin-Serrano, J. (2008). Differential requirements the matrix protein of vesicular stomatitis virus and rabies virus interacts with WW for Alix and ESCRT-III in cytokinesis and HIV-1 release. Proc. Natl. Acad. Sci. USA domains of cellular proteins: implications for viral budding. J. Virol. 73, 2921-2929. 105, 10541-10546. Harty, R. N., Brown, M. E., Wang, G., Huibregtse, J. and Hayes, F. P. (2000). A PPxY Chung, H. Y., Morita, E., von Schwedler, U., Muller, B., Krausslich, H. G. and motif within the VP40 protein of Ebola virus interacts physically and functionally with Sundquist, W. I. (2008). NEDD4L overexpression rescues the release and infectivity a ubiquitin ligase: implications for filovirus budding. Proc. Natl. Acad. Sci. USA 97, of human immunodeficiency virus type 1 constructs lacking PTAP and YPXL late 13871-13876. domains. J. Virol. 82, 4884-4897. Hobel, C. F., Albers, S. V., Driessen, A. J. and Lupas, A. N. (2008). The Sulfolobus Connell, J. W., Lindon, C., Luzio, J. P. and Reid, E. (2009). Spastin couples microtubule solfataricus AAA protein Sso0909, a homologue of the eukaryotic ESCRT Vps4 ATPase. severing to membrane traffic in completion of cytokinesis and secretion. Traffic 10, 42- Biochem. Soc. Trans. 36, 94-98. Horii, M., Shibata, H., Kobayashi, R., Katoh, K., Yorikawa, C., Yasuda, J. and Maki, Craven, R. C., Harty, R. N., Paragas, J., Palese, P. and Wills, J. W. (1999). Late domain M. (2006). CHMP7, a novel ESCRT-III-related protein, associates with CHMP4b and function identified in the vesicular stomatitis virus M protein by use of rhabdovirus- functions in the endosomal sorting pathway. Biochem. J. 400, 23-32. retrovirus chimeras. J. Virol. 73, 3359-3365. Howard, T. L., Stauffer, D. R., Degnin, C. R. and Hollenberg, S. M. (2001). CHMP1 Crump, C. M., Yates, C. and Minson, T. (2007). Herpes simplex virus type 1 cytoplasmic functions as a member of a newly defined family of vesicle trafficking proteins. J. Cell envelopment requires functional Vps4. J. Virol. 81, 7380-7387. Sci. 114, 2395-2404. Demirov, D. G., Ono, A., Orenstein, J. M. and Freed, E. O. (2002). Overexpression of Huang, M., Orenstein, J. M., Martin, M. A. and Freed, E. O. (1995). p6Gag is required the N-terminal domain of TSG101 inhibits HIV-1 budding by blocking late domain for particle production from full-length human immunodeficiency virus type 1 molecular function. Proc. Natl. Acad. Sci. USA 99, 955-960. clones expressing protease. J. Virol. 69, 6810-6818. Dimaano, C., Jones, C. B., Hanono, A., Curtiss, M. and Babst, M. (2008). Ist1 regulates Hurley, J. H. and Emr, S. D. (2006). The ESCRT complexes: structure and mechanism Vps4 localization and assembly. Mol. Biol. Cell 19, 465-474. of a membrane-trafficking network. Annu. Rev. Biophys. Biomol. Struct. 35, 277-298. Dubreuil, V., Marzesco, A. M., Corbeil, D., Huttner, W. B. and Wilsch-Brauninger, Kanazawa, C., Morita, E., Yamada, M., Ishii, N., Miura, S., Asao, H., Yoshimori, T. M. (2007). Midbody and primary cilium of neural progenitors release extracellular and Sugamura, K. (2003). Effects of deficiencies of STAMs and Hrs, mammalian class membrane particles enriched in the stem cell marker prominin-1. J. Cell Biol. 176, 483- E Vps proteins, on receptor downregulation. Biochem. Biophys. Res. Commun. 309, 848-856. Dukes, J. D., Richardson, J. D., Simmons, R. and Whitley, P. (2008). A dominant-negative Katzmann, D. J., Odorizzi, G. and Emr, S. D. (2002). Receptor downregulation and ESCRT-III protein perturbs cytokinesis and trafficking to lysosomes. Biochem. J. 411, multivesicular-body sorting. Nat. Rev. Mol. Cell. Biol. 3, 893-905. 233-239. Katzmann, D. J., Stefan, C. J., Babst, M. and Emr, S. D. (2003). Vps27 recruits ESCRT Eastman, S. W., Martin-Serrano, J., Chung, W., Zang, T. and Bieniasz, P. D. (2005). machinery to endosomes during MVB sorting. J. Cell Biol. 162, 413-423. Identification of human VPS37C, a component of endosomal sorting complex required Kieffer, C., Skalicky, J. J., Morita, E., De Domenico, I., Ward, D. M., Kaplan, J. and for transport-I important for viral budding. J. Biol. Chem. 280, 628-636. Eggert, U. S., Mitchison, T. J. and Field, C. M. (2006). Animal cytokinesis: from parts Sundquist, W. I. (2008). Two distinct modes of ESCRT-III recognition are required for list to mechanisms. Annu. Rev. Biochem. 75, 543-566. VPS4 functions in lysosomal protein targeting and HIV-1 budding. Dev. Cell 15, 62-73. Fabbro, M., Zhou, B. B., Takahashi, M., Sarcevic, B., Lal, P., Graham, M. E., Gabrielli, Kikonyogo, A., Bouamr, F., Vana, M. L., Xiang, Y., Aiyar, A., Carter, C. and Leis, J. B. G., Robinson, P. J., Nigg, E. A., Ono, Y. et al. (2005). Cdk1/Erk2- and Plk1-dependent (2001). Proteins related to the Nedd4 family of ubiquitin protein ligases interact with phosphorylation of a centrosome protein, Cep55, is required for its recruitment to midbody the L domain of Rous sarcoma virus and are required for gag budding from cells. Proc. and cytokinesis. Dev. Cell 9, 477-488. Natl. Acad. Sci. USA 98, 11199-11204. Journal of Cell Science 2176 Journal of Cell Science 122 (13) Kostelansky, M. S., Sun, J., Lee, S., Kim, J., Ghirlando, R., Hierro, A., Emr, S. D. and Parent, L. J., Bennett, R. P., Craven, R. C., Nelle, T. D., Krishna, N. K., Bowzard, J. Hurley, J. H. (2006). Structural and functional organization of the ESCRT-I trafficking B., Wilson, C. B., Puffer, B. A., Montelaro, R. C. and Wills, J. W. (1995). Positionally complex. Cell 125, 113-126. independent and exchangeable late budding functions of the Rous sarcoma virus and Kostelansky, M. S., Schluter, C., Tam, Y. Y., Lee, S., Ghirlando, R., Beach, B., Conibear, human immunodeficiency virus Gag proteins. J. Virol. 69, 5455-5460. E. and Hurley, J. H. (2007). Molecular architecture and functional model of the complete Patnaik, A., Chau, V. and Wills, J. W. (2000). Ubiquitin is part of the retrovirus budding yeast ESCRT-I heterotetramer. Cell 129, 485-498. machinery. Proc. Natl. Acad. Sci. USA 97, 13069-13074. Kouranti, I., Sachse, M., Arouche, N., Goud, B. and Echard, A. (2006). Rab35 regulates Perez, M., Craven, R. C. and de la Torre, J. C. (2003). The small RING finger protein an endocytic recycling pathway essential for the terminal steps of cytokinesis. Curr. Z drives arenavirus budding: implications for antiviral strategies. Proc. Natl. Acad. Sci. Biol. 16, 1719-1725. USA 100, 12978-12983. Lambert, C., Doring, T. and Prange, R. (2007). Hepatitis B virus maturation is sensitive Pineda-Molina, E., Belrhali, H., Piefer, A. J., Akula, I., Bates, P. and Weissenhorn, W. to functional inhibition of ESCRT-III, Vps4, and gamma 2-adaptin. J. Virol. 81, 9050- (2006). The crystal structure of the C-terminal domain of Vps28 reveals a conserved surface required for Vps20 recruitment. Traffic 7, 1007-1016. Langelier, C., von Schwedler, U. K., Fisher, R. D., De Domenico, I., White, P. L., Hill, Pohl, C. and Jentsch, S. (2008). Final stages of cytokinesis and midbody ring formation C. P., Kaplan, J., Ward, D. and Sundquist, W. I. (2006). Human ESCRT-II complex are controlled by BRUCE. Cell 132, 832-845. and its role in human immunodeficiency virus type 1 release. J. Virol. 80, 9465-9480. Popov, S., Popova, E., Inoue, M. and Gottlinger, H. G. (2008). Human immunodeficiency Lata, S., Roessle, M., Solomons, J., Jamin, M., Gottlinger, H. G., Svergun, D. I. and virus type 1 Gag engages the Bro1 domain of ALIX/AIP1 through the nucleocapsid. J. Weissenhorn, W. (2008a). Structural basis for autoinhibition of ESCRT-III CHMP3. J. Virol. 82, 1389-1398. Mol. Biol. 378, 818-827. Pornillos, O., Higginson, D. S., Stray, K. M., Fisher, R. D., Garrus, J. E., Payne, M., Lata, S., Schoehn, G., Jain, A., Pires, R., Piehler, J., Gottlinger, H. G. and Weissenhorn, He, G. P., Wang, H. E., Morham, S. G. and Sundquist, W. I. (2003). HIV Gag mimics W. (2008b). Helical structures of ESCRT-III are disassembled by VPS4. Science 321, the Tsg101-recruiting activity of the human Hrs protein. J. Cell Biol. 162, 425-434. 1354-1357. Prekeris, R. and Gould, G. W. (2008). Breaking up is hard to do-membrane traffic in Le Blanc, I., Prevost, M. C., Dokhelar, M. C. and Rosenberg, A. R. (2002). The PPPY cytokinesis. J. Cell Sci. 121, 1569-1576. motif of human T-cell leukemia virus type 1 Gag protein is required early in the budding Raiborg, C., Malerod, L., Pedersen, N. M. and Stenmark, H. (2008). Differential process. J. Virol. 76, 10024-10029. functions of Hrs and ESCRT proteins in endocytic membrane trafficking. Exp. Cell Res. Lee, H. H., Elia, N., Ghirlando, R., Lippincott-Schwartz, J. and Hurley, J. H. (2008). 314, 801-813. Midbody targeting of the ESCRT machinery by a noncanonical coiled coil in CEP55. Raymond, C. K., Howald-Stevenson, I., Vater, C. A. and Stevens, T. H. (1992). Science 322, 576-580. Morphological classification of the yeast vacuolar protein sorting mutants: evidence for Lin, Y., Kimpler, L. A., Naismith, T. V., Lauer, J. M. and Hanson, P. I. (2005). Interaction a prevacuolar compartment in class E vps mutants. Mol. Biol. Cell 3, 1389-1402. of the mammalian endosomal sorting complex required for transport (ESCRT) III protein Reid, E., Connell, J., Edwards, T. L., Duley, S., Brown, S. E. and Sanderson, C. M. hSnf7-1 with itself, membranes, and the AAA+ ATPase SKD1. J. Biol. Chem. 280, (2005). The hereditary spastic paraplegia protein spastin interacts with the ESCRT-III 12799-12809. complex-associated endosomal protein CHMP1B. Hum. Mol. Genet. 14, 19-38. Lindas, A. C., Karlsson, E. A., Lindgren, M. T., Ettema, T. J. and Bernander, R. (2008). Roll-Mecak, A. and Vale, R. D. (2008). Structural basis of microtubule severing by the A unique cell division machinery in the Archaea. Proc. Natl. Acad. Sci. USA 105, 18942- hereditary spastic paraplegia protein spastin. Nature 451, 363-367. Row, P. E., Liu, H., Hayes, S., Welchman, R., Charalabous, P., Hofmann, K., Clague, Lottridge, J. M., Flannery, A. R., Vincelli, J. L. and Stevens, T. H. (2006). Vta1p and M. J., Sanderson, C. M. and Urbe, S. (2007). The MIT domain of UBPY constitutes Vps46p regulate the membrane association and ATPase activity of Vps4p at the yeast a CHMP binding and endosomal localization signal required for efficient epidermal multivesicular body. Proc. Natl. Acad. Sci. USA 103, 6202-6207. growth factor receptor degradation. J. Biol. Chem. 282, 30929-30937. Low, S. H., Li, X., Miura, M., Kudo, N., Quinones, B. and Weimbs, T. (2003). Syntaxin Rue, S. M., Mattei, S., Saksena, S. and Emr, S. D. (2008). Novel Ist1-Did2 complex 2 and endobrevin are required for the terminal step of cytokinesis in mammalian cells. functions at a late step in multivesicular body sorting. Mol. Biol. Cell 19, 475-484. Dev. Cell 4, 753-759. Saksena, S., Wahlman, J., Teis, D., Johnson, A. E. and Emr, S. D. (2009). Functional Malerod, L., Stuffers, S., Brech, A. and Stenmark, H. (2007). Vps22/EAP30 in ESCRT- reconstitution of ESCRT-III assembly and disassembly. Cell 136, 97-109. II mediates endosomal sorting of growth factor and chemokine receptors destined for Samson, R. Y., Obita, T., Freund, S. M., Williams, R. L. and Bell, S. D. (2008). A role lysosomal degradation. Traffic 8, 1617-1629. for the ESCRT system in cell division in archaea. Science 322, 1710-1713. Martin-Serrano, J. (2007). The role of ubiquitin in retroviral egress. Traffic 8, 1297-1303. Schmidt, M. H., Hoeller, D., Yu, J., Furnari, F. B., Cavenee, W. K., Dikic, I. and Bogler, Martin-Serrano, J., Zang, T. and Bieniasz, P. D. (2001). HIV-1 and Ebola virus encode O. (2004). Alix/AIP1 antagonizes epidermal growth factor receptor downregulation by small peptide motifs that recruit Tsg101 to sites of particle assembly to facilitate egress. the Cbl-SETA/CIN85 complex. Mol. Cell. Biol. 24, 8981-8993. Nat. Med. 7, 1313-1319. Schmitt, A. P., Leser, G. P., Morita, E., Sundquist, W. I. and Lamb, R. A. (2005). Martin-Serrano, J., Yarovoy, A., Perez-Caballero, D. and Bieniasz, P. D. (2003a). Evidence for a new viral late-domain core sequence, FPIV, necessary for budding of a Divergent retroviral late-budding domains recruit vacuolar protein sorting factors by paramyxovirus. J. Virol. 79, 2988-2997. using alternative adaptor proteins. Proc. Natl. Acad. Sci. USA 100, 12414-12419. Schubert, U., Ott, D. E., Chertova, E. N., Welker, R., Tessmer, U., Princiotta, M. F., Martin-Serrano, J., Zang, T. and Bieniasz, P. D. (2003b). Role of ESCRT-I in retroviral Bennink, J. R., Krausslich, H. G. and Yewdell, J. W. (2000). Proteasome inhibition budding. J. Virol. 77, 4794-4804. interferes with gag polyprotein processing, release, and maturation of HIV-1 and HIV- Martin-Serrano, J., Eastman, S. W., Chung, W. and Bieniasz, P. D. (2005). HECT 2. Proc. Natl. Acad. Sci. USA 97, 13057-13062. ubiquitin ligases link viral and cellular PPXY motifs to the vacuolar protein-sorting Scott, A., Chung, H. Y., Gonciarz-Swiatek, M., Hill, G. C., Whitby, F. G., Gaspar, J., pathway. J. Cell Biol. 168, 89-101. Holton, J. M., Viswanathan, R., Ghaffarian, S., Hill, C. P. et al. (2005a). Structural Martinez-Garay, I., Rustom, A., Gerdes, H. H. and Kutsche, K. (2006). The novel and mechanistic studies of VPS4 proteins. EMBO J. 24, 3658-3669. centrosomal associated protein CEP55 is present in the spindle midzone and the midbody. Scott, A., Gaspar, J., Stuchell-Brereton, M. D., Alam, S. L., Skalicky, J. J. and Genomics 87, 243-253. Sundquist, W. I. (2005b). Structure and ESCRT-III protein interactions of the MIT McCullough, J., Clague, M. J. and Urbe, S. (2004). AMSH is an endosome-associated domain of human VPS4A. Proc. Natl. Acad. Sci. USA 102, 13813-13818. ubiquitin isopeptidase. J. Cell Biol. 166, 487-492. Segura-Morales, C., Pescia, C., Chatellard-Causse, C., Sadoul, R., Bertrand, E. and McCullough, J., Fisher, R. D., Whitby, F. G., Sundquist, W. I. and Hill, C. P. (2008). Basyuk, E. (2005). Tsg101 and Alix interact with murine leukemia virus Gag and ALIX-CHMP4 interactions in the human ESCRT pathway. Proc. Natl. Acad. Sci. USA cooperate with Nedd4 ubiquitin ligases during budding. J. Biol. Chem. 280, 27004-27012. 105, 7687-7691. Shim, J. H., Xiao, C., Hayden, M. S., Lee, K. Y., Trombetta, E. S., Pypaert, M., Nara, Morita, E., Sandrin, V., Alam, S. L., Eckert, D. M., Gygi, S. P. and Sundquist, W. I. A., Yoshimori, T., Wilm, B., Erdjument-Bromage, H. et al. (2006). CHMP5 is essential (2007a). Identification of human MVB12 proteins as ESCRT-I subunits that function in for late endosome function and down-regulation of receptor signaling during mouse HIV budding. Cell Host Microbe 2, 41-53. embryogenesis. J. Cell Biol. 172, 1045-1056. Morita, E., Sandrin, V., Chung, H. Y., Morham, S. G., Gygi, S. P., Rodesch, C. K. and Shim, S., Kimpler, L. A. and Hanson, P. I. (2007). Structure/function analysis of four Sundquist, W. I. (2007b). Human ESCRT and ALIX proteins interact with proteins of core ESCRT-III proteins reveals common regulatory role for extreme C-terminal the midbody and function in cytokinesis. EMBO J. 26, 4215-4227. domain. Traffic 8, 1068-1079. Mukai, A., Mizuno, E., Kobayashi, K., Matsumoto, M., Nakayama, K. I., Kitamura, Shim, S., Merrill, S. A. and Hanson, P. I. (2008). Novel interactions of ESCRT-III with N. and Komada, M. (2008). Dynamic regulation of ubiquitylation and deubiquitylation LIP5 and VPS4 and their implications for ESCRT-III disassembly. Mol. Biol. Cell 19, at the central spindle during cytokinesis. J. Cell Sci. 121, 1325-1333. 2661-2672. Muziol, T., Pineda-Molina, E., Ravelli, R. B., Zamborlini, A., Usami, Y., Gottlinger, Stahelin, R. V., Long, F., Diraviyam, K., Bruzik, K. S., Murray, D. and Cho, W. (2002). H. and Weissenhorn, W. (2006). Structural basis for budding by the ESCRT-III factor Phosphatidylinositol 3-phosphate induces the membrane penetration of the FYVE CHMP3. Dev. Cell 10, 821-830. domains of Vps27p and Hrs. J. Biol. Chem. 277, 26379-26388. Nickerson, D. P., West, M. and Odorizzi, G. (2006). Did2 coordinates Vps4-mediated Strack, B., Calistri, A., Accola, M. A., Palu, G. and Gottlinger, H. G. (2000). A role dissociation of ESCRT-III from endosomes. J. Cell Biol. 175, 715-720. for ubiquitin ligase recruitment in retrovirus release. Proc. Natl. Acad. Sci. USA 97, Nickerson, D. P., Russell, M. R. and Odorizzi, G. (2007). A concentric circle model of multivesicular body cargo sorting. EMBO Rep. 8, 644-650. 13063-13068. Obita, T., Saksena, S., Ghazi-Tabatabai, S., Gill, D. J., Perisic, O., Emr, S. D. and Strack, B., Calistri, A., Craig, S., Popova, E. and Gottlinger, H. G. (2003). AIP1/ALIX Williams, R. L. (2007). Structural basis for selective recognition of ESCRT-III by the is a binding partner for HIV-1 p6 and EIAV p9 functioning in virus budding. Cell 114, AAA ATPase Vps4. Nature 449, 735-739. 689-699. Odorizzi, G., Babst, M. and Emr, S. D. (1998). Fab1p PtdIns(3)P 5-kinase function Stuchell, M. D., Garrus, J. E., Muller, B., Stray, K. M., Ghaffarian, S., McKinnon, essential for protein sorting in the multivesicular body. Cell 95, 847-858. R., Krausslich, H. G., Morham, S. G. and Sundquist, W. I. (2004). The human Journal of Cell Science ECSRTs in abscission and viral release 2177 endosomal sorting complex required for transport (ESCRT-I) and its role in HIV-1 White, S. R., Evans, K. J., Lary, J., Cole, J. L. and Lauring, B. (2007). Recognition of budding. J. Biol. Chem. 279, 36059-36071. C-terminal amino acids in tubulin by pore loops in Spastin is important for microtubule Stuchell-Brereton, M. D., Skalicky, J. J., Kieffer, C., Karren, M. A., Ghaffarian, S. severing. J. Cell Biol. 176, 995-1005. and Sundquist, W. I. (2007). ESCRT-III recognition by VPS4 ATPases. Nature 449, Whitley, P., Reaves, B. J., Hashimoto, M., Riley, A. M., Potter, B. V. and Holman, G. 740-744. D. (2003). Identification of mammalian Vps24p as an effector of phosphatidylinositol Tanzi, G. O., Piefer, A. J. and Bates, P. (2003). Equine infectious anemia virus utilizes 3,5-bisphosphate-dependent endosome compartmentalization. J. Biol. Chem. 278, 38786- host vesicular protein sorting machinery during particle release. J. Virol. 77, 8440-8447. 38795. Teis, D., Saksena, S. and Emr, S. D. (2008). Ordered assembly of the ESCRT-III complex Williams, R. L. and Urbe, S. (2007). The emerging shape of the ESCRT machinery. Nat. on endosomes is required to sequester cargo during MVB formation. Dev. Cell 15, 578- Rev. Mol. Cell. Biol. 8, 355-368. 589. Wilson, G. M., Fielding, A. B., Simon, G. C., Yu, X., Andrews, P. D., Hames, R. S., Teo, H., Perisic, O., Gonzalez, B. and Williams, R. L. (2004a). ESCRT-II, an endosome- Frey, A. M., Peden, A. A., Gould, G. W. and Prekeris, R. (2005). The FIP3-Rab11 associated complex required for protein sorting: crystal structure and interactions with protein complex regulates recycling endosome targeting to the cleavage furrow during ESCRT-III and membranes. Dev. Cell 7, 559-569. late cytokinesis. Mol. Biol. Cell 16, 849-860. Teo, H., Veprintsev, D. B. and Williams, R. L. (2004b). Structural insights into endosomal Wollert, T., Wunder, C., Lippincott-Schwartz, J. and Hurley, J. H. (2009a). Membrane sorting complex required for transport (ESCRT-I) recognition of ubiquitinated proteins. scission by the ESCRT-III complex. Nature 458, 172-177. J. Biol. Chem. 279, 28689-28696. Wollert, T., Yang, D., Ren, X., Lee, H. H., Im, Y. J. and Hurley, J. H. (2009b). The Teo, H., Gill, D. J., Sun, J., Perisic, O., Veprintsev, D. B., Vallis, Y., Emr, S. D. and ESCRT machinery at a glance. J. Cell Sci. 122, 2163-2166. Williams, R. L. (2006). ESCRT-I core and ESCRT-II GLUE domain structures reveal Xiao, J., Xia, H., Zhou, J., Azmi, I. F., Davies, B. A., Katzmann, D. J. and Xu, Z. role for GLUE in linking to ESCRT-I and membranes. Cell 125, 99-111. (2008). Structural basis of Vta1 function in the multivesicular body sorting pathway. Tsang, H. T., Connell, J. W., Brown, S. E., Thompson, A., Reid, E. and Sanderson, C. Dev. Cell 14, 37-49. M. (2006). A systematic analysis of human CHMP protein interactions: additional MIT Yang, D., Rismanchi, N., Renvoise, B., Lippincott-Schwartz, J., Blackstone, C. and domain-containing proteins bind to multiple components of the human ESCRT III Hurley, J. H. (2008). Structural basis for midbody targeting of spastin by the ESCRT- complex. Genomics 88, 333-346. III protein CHMP1B. Nat. Struct. Mol. Biol. 15, 1278-1286. Urbe, S., Sachse, M., Row, P. E., Preisinger, C., Barr, F. A., Strous, G., Klumperman, Yasuda, J., Hunter, E., Nakao, M. and Shida, H. (2002). Functional involvement of a J. and Clague, M. J. (2003). The UIM domain of Hrs couples receptor sorting to vesicle novel Nedd4-like ubiquitin ligase on retrovirus budding. EMBO Rep. 3, 636-640. formation. J. Cell Sci. 116, 4169-4179. Yorikawa, C., Shibata, H., Waguri, S., Hatta, K., Horii, M., Katoh, K., Kobayashi, T., Usami, Y., Popov, S. and Gottlinger, H. G. (2007). Potent rescue of human Uchiyama, Y. and Maki, M. (2005). Human CHMP6, a myristoylated ESCRT-III immunodeficiency virus type 1 late domain mutants by ALIX/AIP1 depends on its protein, interacts directly with an ESCRT-II component EAP20 and regulates endosomal CHMP4 binding site. J. Virol. 81, 6614-6622. cargo sorting. Biochem. J. 387, 17-26. Usami, Y., Popov, S., Popova, E. and Gottlinger, H. G. (2008). Efficient and specific Yu, X., Prekeris, R. and Gould, G. W. (2007). Role of endosomal Rab GTPases in rescue of human immunodeficiency virus type 1 budding defects by a Nedd4-like cytokinesis. Eur. J. Cell Biol. 86, 25-35. ubiquitin ligase. J. Virol. 82, 4898-4907. Yu, Z., Gonciarz, M. D., Sundquist, W. I., Hill, C. P. and Jensen, G. J. (2008). Cryo- VerPlank, L., Bouamr, F., LaGrassa, T. J., Agresta, B., Kikonyogo, A., Leis, J. and EM structure of dodecameric Vps4p and its 2:1 complex with Vta1p. J. Mol. Biol. 377, Carter, C. A. (2001). Tsg101, a homologue of ubiquitin-conjugating (E2) enzymes, 364-377. binds the L domain in HIV type 1 Pr55(Gag). Proc. Natl. Acad. Sci. USA 98, 7724- Yuan, B., Campbell, S., Bacharach, E., Rein, A. and Goff, S. P. (2000). Infectivity of 7729. Moloney murine leukemia virus defective in late assembly events is restored by late von Schwedler, U. K., Stuchell, M., Muller, B., Ward, D. M., Chung, H. Y., Morita, assembly domains of other retroviruses. J. Virol. 74, 7250-7260. E., Wang, H. E., Davis, T., He, G. P., Cimbora, D. M. et al. (2003). The protein Zamborlini, A., Usami, Y., Radoshitzky, S. R., Popova, E., Palu, G. and Gottlinger, network of HIV budding. Cell 114, 701-713. H. (2006). Release of autoinhibition converts ESCRT-III components into potent Ward, D. M., Vaughn, M. B., Shiflett, S. L., White, P. L., Pollock, A. L., Hill, J., inhibitors of HIV-1 budding. Proc. Natl. Acad. Sci. USA 103, 19140-19145. Schnegelberger, R., Sundquist, W. I. and Kaplan, J. (2005). The role of LIP5 and Zhai, Q., Fisher, R. D., Chung, H. Y., Myszka, D. G., Sundquist, W. I. and Hill, C. P. CHMP5 in multivesicular body formation and HIV-1 budding in mammalian cells. J. (2008). Structural and functional studies of ALIX interactions with YPX(n)L late domains Biol. Chem. 280, 10548-10555. of HIV-1 and EIAV. Nat. Struct. Mol. Biol. 15, 43-49. Watanabe, T., Sorensen, E. M., Naito, A., Schott, M., Kim, S. and Ahlquist, P. (2007). Zhao, W. M., Seki, A. and Fang, G. (2006). Cep55, a microtubule-bundling protein, Involvement of host cellular multivesicular body functions in hepatitis B virus budding. associates with centralspindlin to control the midbody integrity and cell abscission during Proc. Natl. Acad. Sci. USA 104, 10205-10210. cytokinesis. Mol. Biol. Cell 17, 3881-3896. Journal of Cell Science
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Journal of Cell Science – The Company of Biologists
Published: Jul 1, 2009