Nature Reviews Molecular Cell Biology

D’Angelo, Gisela; Raposo, Graça; Nishimura, Tamako; Suetsugu, Shiro

doi: 10.1038/s41580-022-00555-xpmid: 36280788

Cellular protrusions are highly dynamic structures that facilitate cell–cell communication and are increasingly recognised for their roles in the shedding of bioactive extracellular vesicles (EVs). The intrinsic and extrinsic mechanisms that govern the shedding of EVs from cellular protrusions and their potential physiological roles are beginning to emerge.

Zlotorynski, Eytan

doi: 10.1038/s41580-022-00575-7pmid: 36609652

Early zebrafish embryos increase the size and complexity of their nuclear pore complexes, enabling efficient nuclear import of maternal transcription factors, which induces zygotic genome activation.

Strzyz, Paulina

doi: 10.1038/s41580-022-00570-ypmid: 36536115

Zhang et al. report that angiogenesis in the chick embryo is supported by migrasomes — recently described organelles produced by migrating cells.

Heinke, Lisa

doi: 10.1038/s41580-022-00574-8pmid: 36600033

Fong et al. describe a novel complex that links between H3K9 methylation and H3K27 methylation and has a role in gene silencing and cancer.

Sun, Liming

doi: 10.1038/s41580-022-00553-zpmid: 36266548

Liming Sun brings to attention paper by Li et al. (2012) reporting that necroptosis kinases, RIPK1 and RIPK3, form functional amyloids that regulate cell death signalling.

Chen, Leilei

doi: 10.1038/s41580-022-00540-4pmid: 36076034

Leilei Chen describes the discovery that adenosine-to-inosine editing by ADAR1 marks endogenous double-stranded RNA as self, to prevent it from triggering innate immunity.

Linder, Stefan; Cervero, Pasquale; Eddy, Robert; Condeelis, John

doi: 10.1038/s41580-022-00530-6pmid: 36104625

Cell invasion into the surrounding extracellular matrix or across tissue boundaries and endothelial barriers occurs in both physiological and pathological scenarios such as immune surveillance or cancer metastasis. Podosomes and invadopodia, collectively called ‘invadosomes’, are actin-based structures that drive the proteolytic invasion of cells, by forming highly regulated platforms for the localized release of lytic enzymes that degrade the matrix. Recent advances in high-resolution microscopy techniques, in vivo imaging and high-throughput analyses have led to considerable progress in understanding mechanisms of invadosomes, revealing the intricate inner architecture of these structures, as well as their growing repertoire of functions that extends well beyond matrix degradation. In this Review, we discuss the known functions, architecture and regulatory mechanisms of podosomes and invadopodia. In particular, we describe the molecular mechanisms of localized actin turnover and microtubule-based cargo delivery, with a special focus on matrix-lytic enzymes that enable proteolytic invasion. Finally, we point out topics that should become important in the invadosome field in the future.

Levental, Ilya; Lyman, Ed

doi: 10.1038/s41580-022-00524-4pmid: 36056103

Transmembrane proteins comprise ~30% of the mammalian proteome, mediating metabolism, signalling, transport and many other functions required for cellular life. The microenvironment of integral membrane proteins (IMPs) is intrinsically different from that of cytoplasmic proteins, with IMPs solvated by a compositionally and biophysically complex lipid matrix. These solvating lipids affect protein structure and function in a variety of ways, from stereospecific, high-affinity protein–lipid interactions to modulation by bulk membrane properties. Specific examples of functional modulation of IMPs by their solvating membranes have been reported for various transporters, channels and signal receptors; however, generalizable mechanistic principles governing IMP regulation by lipid environments are neither widely appreciated nor completely understood. Here, we review recent insights into the inter-relationships between complex lipidomes of mammalian membranes, the membrane physicochemical properties resulting from such lipid collectives, and the regulation of IMPs by either or both. The recent proliferation of high-resolution methods to study such lipid–protein interactions has led to generalizable insights, which we synthesize into a general framework termed the ‘functional paralipidome’ to understand the mutual regulation between membrane proteins and their surrounding lipid microenvironments.

Wang, Xin; Ramat, Anne; Simonelig, Martine; Liu, Mo-Fang

doi: 10.1038/s41580-022-00528-0pmid: 36104626

PIWI-interacting RNAs (piRNAs) are a class of small non-coding RNAs that associate with proteins of the PIWI clade of the Argonaute family. First identified in animal germ line cells, piRNAs have essential roles in germ line development. The first function of PIWI–piRNA complexes to be described was the silencing of transposable elements, which is crucial for maintaining the integrity of the germ line genome. Later studies provided new insights into the functions of PIWI–piRNA complexes by demonstrating that they regulate protein-coding genes. Recent studies of piRNA biology, including in new model organisms such as golden hamsters, have deepened our understanding of both piRNA biogenesis and piRNA function. In this Review, we discuss the most recent advances in our understanding of piRNA biogenesis, the molecular mechanisms of piRNA function and the emerging roles of piRNAs in germ line development mainly in flies and mice, and in infertility, cancer and neurological diseases in humans.

Kanchanawong, Pakorn; Calderwood, David A.

doi: 10.1038/s41580-022-00531-5pmid: 36168065

The ability of animal cells to sense, adhere to and remodel their local extracellular matrix (ECM) is central to control of cell shape, mechanical responsiveness, motility and signalling, and hence to development, tissue formation, wound healing and the immune response. Cell–ECM interactions occur at various specialized, multi-protein adhesion complexes that serve to physically link the ECM to the cytoskeleton and the intracellular signalling apparatus. This occurs predominantly via clustered transmembrane receptors of the integrin family. Here we review how the interplay of mechanical forces, biochemical signalling and molecular self-organization determines the composition, organization, mechanosensitivity and dynamics of these adhesions. Progress in the identification of core multi-protein modules within the adhesions and characterization of rearrangements of their components in response to force, together with advanced imaging approaches, has improved understanding of adhesion maturation and turnover and the relationships between adhesion structures and functions. Perturbations of adhesion contribute to a broad range of diseases and to age-related dysfunction, thus an improved understanding of their molecular nature may facilitate therapeutic intervention in these conditions.