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Philosophical Transactions of the Royal Society B: Biological Sciences logoLink to Philosophical Transactions of the Royal Society B: Biological Sciences
. 2003 May 29;358(1433):863–868. doi: 10.1098/rstb.2003.1274

Formation of functional cell membrane domains: the interplay of lipid- and protein-mediated interactions.

Thomas Harder 1
PMCID: PMC1693179  PMID: 12803918

Abstract

Numerous cell membrane associated processes, including signal transduction, membrane sorting, protein processing and virus trafficking take place in membrane subdomains. Protein-protein interactions provide the frameworks necessary to generate biologically functional membrane domains. For example, coat proteins define membrane areas destined for sorting processes, viral proteins self-assemble to generate a budding virus, and adapter molecules organize multimolecular signalling assemblies, which catalyse downstream reactions. The concept of raft lipid-based membrane domains provides a different principle for compartmentalization and segregation of membrane constituents. Accordingly, rafts are defined by the physical properties of the lipid bilayer and function by selective partitioning of membrane lipids and proteins into membrane domains of specific phase behaviour and lipid packing. Here, I will discuss the interplay of these independent principles of protein scaffolds and raft lipid microdomains leading to the generation of biologically functional membrane domains.

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Selected References

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  1. Alfsen A., Iniguez P., Bouguyon E., Bomsel M. Secretory IgA specific for a conserved epitope on gp41 envelope glycoprotein inhibits epithelial transcytosis of HIV-1. J Immunol. 2001 May 15;166(10):6257–6265. doi: 10.4049/jimmunol.166.10.6257. [DOI] [PubMed] [Google Scholar]
  2. Almeida P. F., Vaz W. L., Thompson T. E. Lateral diffusion in the liquid phases of dimyristoylphosphatidylcholine/cholesterol lipid bilayers: a free volume analysis. Biochemistry. 1992 Jul 28;31(29):6739–6747. doi: 10.1021/bi00144a013. [DOI] [PubMed] [Google Scholar]
  3. Brown D. A., London E. Structure and origin of ordered lipid domains in biological membranes. J Membr Biol. 1998 Jul 15;164(2):103–114. doi: 10.1007/s002329900397. [DOI] [PubMed] [Google Scholar]
  4. Brown D. A., London E. Structure of detergent-resistant membrane domains: does phase separation occur in biological membranes? Biochem Biophys Res Commun. 1997 Nov 7;240(1):1–7. doi: 10.1006/bbrc.1997.7575. [DOI] [PubMed] [Google Scholar]
  5. Brown D. A., Rose J. K. Sorting of GPI-anchored proteins to glycolipid-enriched membrane subdomains during transport to the apical cell surface. Cell. 1992 Feb 7;68(3):533–544. doi: 10.1016/0092-8674(92)90189-j. [DOI] [PubMed] [Google Scholar]
  6. Bunnell Stephen C., Hong David I., Kardon Julia R., Yamazaki Tetsuo, McGlade C. Jane, Barr Valarie A., Samelson Lawrence E. T cell receptor ligation induces the formation of dynamically regulated signaling assemblies. J Cell Biol. 2002 Sep 30;158(7):1263–1275. doi: 10.1083/jcb.200203043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Burack W. Richard, Lee Kyeong-Hee, Holdorf Amy D., Dustin Michael L., Shaw Andrey S. Cutting edge: quantitative imaging of raft accumulation in the immunological synapse. J Immunol. 2002 Sep 15;169(6):2837–2841. doi: 10.4049/jimmunol.169.6.2837. [DOI] [PubMed] [Google Scholar]
  8. Dietrich Christian, Yang Bing, Fujiwara Takahiro, Kusumi Akihiro, Jacobson Ken. Relationship of lipid rafts to transient confinement zones detected by single particle tracking. Biophys J. 2002 Jan;82(1 Pt 1):274–284. doi: 10.1016/S0006-3495(02)75393-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Drevot Philippe, Langlet Claire, Guo Xiao-Jun, Bernard Anne-Marie, Colard Odile, Chauvin Jean-Paul, Lasserre Rémi, He Hai-Tao. TCR signal initiation machinery is pre-assembled and activated in a subset of membrane rafts. EMBO J. 2002 Apr 15;21(8):1899–1908. doi: 10.1093/emboj/21.8.1899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Friedrichson T., Kurzchalia T. V. Microdomains of GPI-anchored proteins in living cells revealed by crosslinking. Nature. 1998 Aug 20;394(6695):802–805. doi: 10.1038/29570. [DOI] [PubMed] [Google Scholar]
  11. Gómez-Móuton C., Abad J. L., Mira E., Lacalle R. A., Gallardo E., Jiménez-Baranda S., Illa I., Bernad A., Mañes S., Martínez-A C. Segregation of leading-edge and uropod components into specific lipid rafts during T cell polarization. Proc Natl Acad Sci U S A. 2001 Aug 7;98(17):9642–9647. doi: 10.1073/pnas.171160298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Harder T., Kuhn M. Selective accumulation of raft-associated membrane protein LAT in T cell receptor signaling assemblies. J Cell Biol. 2000 Oct 16;151(2):199–208. doi: 10.1083/jcb.151.2.199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Harder T., Scheiffele P., Verkade P., Simons K. Lipid domain structure of the plasma membrane revealed by patching of membrane components. J Cell Biol. 1998 May 18;141(4):929–942. doi: 10.1083/jcb.141.4.929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kenworthy A. K., Petranova N., Edidin M. High-resolution FRET microscopy of cholera toxin B-subunit and GPI-anchored proteins in cell plasma membranes. Mol Biol Cell. 2000 May;11(5):1645–1655. doi: 10.1091/mbc.11.5.1645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kropshofer H., Spindeldreher S., Röhn T. A., Platania N., Grygar C., Daniel N., Wölpl A., Langen H., Horejsi V., Vogt A. B. Tetraspan microdomains distinct from lipid rafts enrich select peptide-MHC class II complexes. Nat Immunol. 2001 Dec 17;3(1):61–68. doi: 10.1038/ni750. [DOI] [PubMed] [Google Scholar]
  16. Kurzchalia T. V., Parton R. G. Membrane microdomains and caveolae. Curr Opin Cell Biol. 1999 Aug;11(4):424–431. doi: 10.1016/s0955-0674(99)80061-1. [DOI] [PubMed] [Google Scholar]
  17. Lindwasser O. W., Resh M. D. Multimerization of human immunodeficiency virus type 1 Gag promotes its localization to barges, raft-like membrane microdomains. J Virol. 2001 Sep;75(17):7913–7924. doi: 10.1128/JVI.75.17.7913-7924.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. London Erwin. Insights into lipid raft structure and formation from experiments in model membranes. Curr Opin Struct Biol. 2002 Aug;12(4):480–486. doi: 10.1016/s0959-440x(02)00351-2. [DOI] [PubMed] [Google Scholar]
  19. Mayor S., Rothberg K. G., Maxfield F. R. Sequestration of GPI-anchored proteins in caveolae triggered by cross-linking. Science. 1994 Jun 24;264(5167):1948–1951. doi: 10.1126/science.7516582. [DOI] [PubMed] [Google Scholar]
  20. Mañes S., del Real G., Lacalle R. A., Lucas P., Gómez-Moutón C., Sánchez-Palomino S., Delgado R., Alcamí J., Mira E., Martínez-A C. Membrane raft microdomains mediate lateral assemblies required for HIV-1 infection. EMBO Rep. 2000 Aug;1(2):190–196. doi: 10.1093/embo-reports/kvd025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Melkonian K. A., Ostermeyer A. G., Chen J. Z., Roth M. G., Brown D. A. Role of lipid modifications in targeting proteins to detergent-resistant membrane rafts. Many raft proteins are acylated, while few are prenylated. J Biol Chem. 1999 Feb 5;274(6):3910–3917. doi: 10.1074/jbc.274.6.3910. [DOI] [PubMed] [Google Scholar]
  22. Pelkmans L., Kartenbeck J., Helenius A. Caveolar endocytosis of simian virus 40 reveals a new two-step vesicular-transport pathway to the ER. Nat Cell Biol. 2001 May;3(5):473–483. doi: 10.1038/35074539. [DOI] [PubMed] [Google Scholar]
  23. Pralle A., Keller P., Florin E. L., Simons K., Hörber J. K. Sphingolipid-cholesterol rafts diffuse as small entities in the plasma membrane of mammalian cells. J Cell Biol. 2000 Mar 6;148(5):997–1008. doi: 10.1083/jcb.148.5.997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Resh M. D. Fatty acylation of proteins: new insights into membrane targeting of myristoylated and palmitoylated proteins. Biochim Biophys Acta. 1999 Aug 12;1451(1):1–16. doi: 10.1016/s0167-4889(99)00075-0. [DOI] [PubMed] [Google Scholar]
  25. Rinia H. A., Snel M. M., van der Eerden J. P., de Kruijff B. Visualizing detergent resistant domains in model membranes with atomic force microscopy. FEBS Lett. 2001 Jul 13;501(1):92–96. doi: 10.1016/s0014-5793(01)02636-9. [DOI] [PubMed] [Google Scholar]
  26. Röper K., Corbeil D., Huttner W. B. Retention of prominin in microvilli reveals distinct cholesterol-based lipid micro-domains in the apical plasma membrane. Nat Cell Biol. 2000 Sep;2(9):582–592. doi: 10.1038/35023524. [DOI] [PubMed] [Google Scholar]
  27. Sankaram M. B., Thompson T. E. Cholesterol-induced fluid-phase immiscibility in membranes. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8686–8690. doi: 10.1073/pnas.88.19.8686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Scheiffele P., Roth M. G., Simons K. Interaction of influenza virus haemagglutinin with sphingolipid-cholesterol membrane domains via its transmembrane domain. EMBO J. 1997 Sep 15;16(18):5501–5508. doi: 10.1093/emboj/16.18.5501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Schroeder R. J., Ahmed S. N., Zhu Y., London E., Brown D. A. Cholesterol and sphingolipid enhance the Triton X-100 insolubility of glycosylphosphatidylinositol-anchored proteins by promoting the formation of detergent-insoluble ordered membrane domains. J Biol Chem. 1998 Jan 9;273(2):1150–1157. doi: 10.1074/jbc.273.2.1150. [DOI] [PubMed] [Google Scholar]
  30. Seveau S., Eddy R. J., Maxfield F. R., Pierini L. M. Cytoskeleton-dependent membrane domain segregation during neutrophil polarization. Mol Biol Cell. 2001 Nov;12(11):3550–3562. doi: 10.1091/mbc.12.11.3550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Simons K., Ikonen E. Functional rafts in cell membranes. Nature. 1997 Jun 5;387(6633):569–572. doi: 10.1038/42408. [DOI] [PubMed] [Google Scholar]
  32. Thomas J. L., Holowka D., Baird B., Webb W. W. Large-scale co-aggregation of fluorescent lipid probes with cell surface proteins. J Cell Biol. 1994 May;125(4):795–802. doi: 10.1083/jcb.125.4.795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Xu X., London E. The effect of sterol structure on membrane lipid domains reveals how cholesterol can induce lipid domain formation. Biochemistry. 2000 Feb 8;39(5):843–849. doi: 10.1021/bi992543v. [DOI] [PubMed] [Google Scholar]
  34. Zacharias David A., Violin Jonathan D., Newton Alexandra C., Tsien Roger Y. Partitioning of lipid-modified monomeric GFPs into membrane microdomains of live cells. Science. 2002 May 3;296(5569):913–916. doi: 10.1126/science.1068539. [DOI] [PubMed] [Google Scholar]
  35. Zhang J., Pekosz A., Lamb R. A. Influenza virus assembly and lipid raft microdomains: a role for the cytoplasmic tails of the spike glycoproteins. J Virol. 2000 May;74(10):4634–4644. doi: 10.1128/jvi.74.10.4634-4644.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Zhang W., Trible R. P., Samelson L. E. LAT palmitoylation: its essential role in membrane microdomain targeting and tyrosine phosphorylation during T cell activation. Immunity. 1998 Aug;9(2):239–246. doi: 10.1016/s1074-7613(00)80606-8. [DOI] [PubMed] [Google Scholar]
  37. van den Berg C. W., Cinek T., Hallett M. B., Horejsi V., Morgan B. P. Exogenous glycosyl phosphatidylinositol-anchored CD59 associates with kinases in membrane clusters on U937 cells and becomes Ca(2+)-signaling competent. J Cell Biol. 1995 Nov;131(3):669–677. doi: 10.1083/jcb.131.3.669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. van't Hof W., Resh M. D. Rapid plasma membrane anchoring of newly synthesized p59fyn: selective requirement for NH2-terminal myristoylation and palmitoylation at cysteine-3. J Cell Biol. 1997 Mar 10;136(5):1023–1035. doi: 10.1083/jcb.136.5.1023. [DOI] [PMC free article] [PubMed] [Google Scholar]

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