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Cited by 2,344

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Structure and Function of Sphingolipid- and Cholesterol-rich Membrane Rafts

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Brown, Deborah A., London, Erwin·2000·Journal of Biological Chemistry
DOI 10.1074/jbc.r000005200
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Abstract

melting temperature liquid crystalline liquid disordered liquid ordered phosphatidylethanolamine phosphatidylcholine detergent-resistant membrane glycosylphosphatidylinositol palmitoyl oleoyl PC T cell receptor It is well known that separate domains with different lipid compositions can exist in liposomes containing mixtures of different phospholipids. The question of whether cellular membranes contain similar lipid domains has intrigued workers for many years. One type of domain, sphingolipid and cholesterol-based structures called membrane rafts, has received much attention in the last few years. We will review the evidence that rafts exist in cells and focus on their structure, or the organization of raft lipids and proteins. Our discussion of function will focus on the role of rafts in signaling in hematopoietic cells, a particularly well developed area that has provided insights into raft organization in the membrane. Several reviews of rafts (1.Simons K. Ikonen E. Nature. 1997; 387: 569-572Crossref PubMed Scopus (8283) Google Scholar, 2.Brown D.A. London E. Annu. Rev. Cell Dev. Biol. 1998; 14: 111-136Crossref PubMed Scopus (2572) Google Scholar, 3.Brown D.A. London E. J. Membr. Biol. 1998; 164: 103-114Crossref PubMed Scopus (850) Google Scholar, 4.Jacobson K. Dietrich C. Trends Cell Biol. 1999; 9: 87-91Abstract Full Text Full Text PDF PubMed Scopus (381) Google Scholar) and of related structures called caveolae (5.Anderson R.G.W. Annu. Rev. Biochem. 1998; 67: 199-225Crossref PubMed Scopus (1741) Google Scholar, 6.Kurzchalia T.V. Parton R.G. Curr. Opin. Cell Biol. 1999; 11: 424-431Crossref PubMed Scopus (516) Google Scholar, 7.Smart E.J. Graf G.A. McNiven M.A. Sessa W.C. Engelman J.A. Scherer P.E. Okamoto T. Lisanti M.P. Mol. Cell. Biol. 1999; 19: 7289-7304Crossref PubMed Scopus (929) Google Scholar) have appeared recently. Sphingolipids differ from most biological phospholipids in containing long, largely saturated acyl chains. This allows them to readily pack tightly together, a property that gives sphingolipids much higher melting temperatures (Tm)1 than membrane (glycero)phospholipids, which are rich in kinked unsaturated acyl chains. It is now clear that tight acyl chain packing is a key feature of raft lipid organization (3.Brown D.A. London E. J. Membr. Biol. 1998; 164: 103-114Crossref PubMed Scopus (850) Google Scholar, 8.Ahmed S.N. Brown D.A. London E. Biochemistry. 1997; 36: 10944-10953Crossref PubMed Scopus (621) Google Scholar, 9.Schroeder R.J. Ahmed S.N. Zhu Y. London E. Brown D.A. J. Biol. Chem. 1998; 273: 1150-1157Abstract Full Text Full Text PDF PubMed Scopus (376) Google Scholar). In fact, the differential packing ability of sphingolipids and phospholipids probably leads to phase separation in the membrane. Thus, sphingolipid-rich rafts co-exist with phospholipid-rich domains that are in the familiar, loosely packed disordered state (variously abbreviated as Lα, lc, or ld). Phase separation between lipids in different physical states, most often the lc and the solid-like gel phases, has been well characterized in model membranes. Indeed, the gel phase is the most familiar state in which acyl chains are highly ordered. However, because of the high concentration of cholesterol in the plasma membrane and other membranes in which rafts form, raft lipids do not exist in the gel phase. Cholesterol has important effects on phase behavior. It is well known that addition of cholesterol to a pure phospholipid bilayer abolishes the normal sharp thermal transition between gel and lc phases, giving the membrane properties intermediate between the two phases. This effect initially suggested that domains in ordered and disordered states cannot co-exist at high cholesterol levels. However, further work showed that a different kind of phase separation can occur in binary mixtures of individual phospholipids with cholesterol. In these mixtures, domains in an lc-like phase co-exist with domains in a new state, the liquid-ordered (lo) phase. Acyl chains of lipids in the lo phase are extended and tightly packed, as in the gel phase, but have a high degree of lateral mobility (3.Brown D.A. London E. J. Membr. Biol. 1998; 164: 103-114Crossref PubMed Scopus (850) Google Scholar). Rafts probably exist in the lo phase or a state with similar properties. In support of this model, detergent-insoluble membranes that can be isolated from cell lysates and are likely to be derived from rafts (discussed below) are in the lo phase (10.Ge M. Field K.A. Aneja R. Holowka D. Baird B. Freed J. Biophys. J. 1999; 77: 925-933Abstract Full Text Full Text PDF PubMed Scopus (116) Google Scholar, 11.Ostermeyer A.G. Beckrich B.T. Ivarson K.A. Grove K.E. Brown D.A. J. Biol. Chem. 1999; 274: 34459-34466Abstract Full Text Full Text PDF PubMed Scopus (151) Google Scholar). Model membrane studies that do not involve detergents also support the idea that lo phase and lc phase domains could co-exist in biological membranes. These studies

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Metadata

Authors
Brown, D. A., & London, E.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2000-06
Volume
275
Issue
23
Pages
17221-17224
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.r000005200
OpenAlex
W2065886456
Cited by
2,344
References
2
FWCI
56.10
Type
journal article
Language
en
Open access
hybrid

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