Review
Sphingolipid transport in eukaryotic cells
Gerrit van Meer *, Joost C.M. Holthuis
Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam,
The Netherlands
Received 27 October 1999; received in revised form 9 November 1999; accepted 9 November 1999
Abstract
Sphingolipids constitute a sizeable fraction of the membrane lipids in all eukaryotes and are indispensable for eukaryotic
life. First of all, the involvement of sphingolipids in organizing the lateral domain structure of membranes appears essential
for processes like protein sorting and membrane signaling. In addition, recognition events between complex glyco-
sphingolipids and glycoproteins are thought to be required for tissue differentiation in higher eukaryotes and for other
specific cell interactions. Finally, upon certain stimuli like stress or receptor activation, sphingolipids give rise to a variety of
second messengers with effects on cellular homeostasis. All sphingolipid actions are governed by their local concentration.
The intricate control of their intracellular topology by the proteins responsible for their synthesis, hydrolysis and intracellular
transport is the topic of this review. ß 2000 Elsevier Science B.V. All rights reserved.
Keywords: Sphingomyelin; Inositolsphingolipid; Glycosphingolipid ; Glycolipid; Translocation; Animal cell ; Yeast
1. Introduction
Eukaryotic cells contain multiple membrane-
bound compartments whose specialized functions re-
quire distinct protein and lipid compositions. Assem-
bly of the correct mixture of proteins and lipids into
each compartment requires a three-step process in-
volving (1) the biosynthesis of proteins and lipids, (2)
selective transport of proteins and lipids across the
compartmental bilayer (intracompartmental trans-
port), and (3) selective transport of proteins and lip-
ids between di¡erent compartments (intercompart-
mental transport; see Fig. 1). Experimental work
over the last 15 years has brought us detailed knowl-
edge concerning the molecular mechanisms responsi-
ble for intra- and intercompartmental protein trans-
port. In contrast, our insight into how lipids are
sorted and moved within cells is far more limited.
This is partially due to the fact that the tra¤cking
rules that apply to lipids are less absolute than those
for proteins, and therefore more di¤cult to translate
into molecular terms. On the other hand, it is becom-
ing increasingly clear that directional transport of at
least some protein and lipid species is controlled by
intricate sorting machineries. A striking example are
the sphingolipid^cholesterol microdomains, called
1388-1981 / 00 / $ ^ see front matter ß 2000 Elsevier Science B.V. All rights reserved.
PII: S1388-1981(00)00054-8
Abbreviations: Cer, ceramide; CGlcT, ceramide glucosyltrans-
ferase; GalCer, galactosylceramide; GalNAc, N-acetylgalactos-
amine; GlcCer, glucosylceramide; GPI, glycosylphosphatidylino-
sitol; IPC, inositolphosphoceramide; MIPC, mannosyl-
inositolphosphoceramide; M(IP)
2
C, inositolphospho-mannosyl-
inositolphosphoceramide; SM, sphingomyelin; TGN, trans-Golgi
network; Glycosphingolipid designation according to the recom-
mendations of the IUPAC-IUB Joint Commission on Biochem-
ical Nomenclature [1], using the Svennerholm abbreviations for
gangliosides and using sulfatide to indicate HSO
3
-3 Gal L1-1 Cer
* Corresponding author. Fax: +31-20-6974156;
E-mail: g.vanmeer@amc.uva.nl
BBAMCB 55632 25-5-00
Biochimica et Biophysica Acta 1486 (2000) 145^170
www.elsevier.com/locate/bba