Skip to main content
SpringerLink
Log in

From Intramolecular Asymmetries to Raft Assemblies

A Short Guide for the Puzzled in Lipidomics

  • Chapter
Membrane Microdomain Signaling

Abstract

For the first-time explorer in biology, lipids are perceived as the building blocks of a barrier that living cells must have in order to maintain their internal milieu of organelles, macromolecules, and solutes in a dynamic steady state. Although this view is generally correct, emerging evidence indicates that many lipids fulfill important regulatory roles and participate actively in cellular signaling. Furthermore, studies based on natural and model membranes suggest that transient and long-lived associations between lipids in the plane of the membrane give rise to yet another dynamic feature of these building blocks: the creation of functional domains in the barrier without which cells may not be able to function appropriately. In this context, the asymmetry between the two leaflets of the plasma membrane (Bretscher, 1973) or the lateral segregation into functional domains on the same leaflet (Brown and London, 2000) suggest a high diversity among lipid constituents. The aim of this chapter is to emphasize that the molecular basis for segregation into rafts or related structures stems from the unique intramolecular asymmetry conferred upon the lipid molecule by its various constituents.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Anderson R. E., Maude M. B., Alvarez R. A., Acland G., and Aguirre G. D. (1999) A hypothesis to explain the reduced blood levels of docosahexaenoic acid in inherited retinal degenerations caused by mutations in genes encoding retina-specific proteins. Lipids 34, S235–237.

    Article  PubMed  CAS  Google Scholar 

  • Anderson R. G. W. and Jacobson K. (2002) A role of lipid shells in targeting proteins to caveolae rafts and other lipid domains. Science 296, 1821–1825.

    Article  PubMed  CAS  Google Scholar 

  • Balasubramanian K. and Schroit A. J. (2003) Aminophospholipid asymmetry; A matter of life and death. Ann. Rev. Physiol. 65, 701–734.

    Article  CAS  Google Scholar 

  • Barenholz Y. and Cevc G. (2000) Physical chemistry of biological surfaces, In, Baszkin A. and Norde W., eds., Marcel Dekker, New York, pp. 171–241.

    Google Scholar 

  • Barker D. J. and Clark P. M. (1997) Fetal undernutrition and disease in later life. Rev. Reprod. 2, 105–112.

    Article  PubMed  CAS  Google Scholar 

  • Bazan N. G. and Rodriguez de Turco E. B. (1994) Pharmacological manipulation of docosahexaenoic-phospholipid biosynthesis in photoreceptor cells: implications in retinal degeneration. J. Ocul. Pharmacol. 10, 591–604.

    PubMed  CAS  Google Scholar 

  • Bevers E. M., Comfurius P., Dekkers D. W. C., and Zwaal R. F. A. (1999) Lipid translocation across the plasma membrane of mammalian cells. Biochim. Biophys. Acta 1439, 317–330.

    PubMed  CAS  Google Scholar 

  • Boon J. M. and Smith B. D. (2002) Chemical control of phospholipid distribution across bilayer membranes. Med. Res. Rev. 22, 251–281.

    Article  PubMed  CAS  Google Scholar 

  • Brand A., Gil S., and Yavin E. (2000) N-Methyl bases of ethanolamine prevent apoptotic cell death induced by oxidative stress in cells of oligodendroglia origin. J. Neurochem. 74, 1596–1604.

    Article  PubMed  CAS  Google Scholar 

  • Brand A. and Yavin E. (2001) Early ethanolamine phospholipid translocation marks stress-induced apoptotic cell death in oligodendroglial cells. J. Neurochem. 78, 1208–1218.

    Article  PubMed  CAS  Google Scholar 

  • Bratton D. L., Fadok V. A., Richter D. A., Kailey J. M., Guthrie L. A., and Henson P. M. (1997) Appearance of phosphatidylserine on apoptotic cells requires calcium-mediated nonspecific flip-flop and is enhanced by loss of the aminophospholipid translocase. J. Biol. Chem. 272, 26,159–26,165.

    Article  PubMed  CAS  Google Scholar 

  • Bretscher M. S. (1973) Membrane structure: some general principles. Science 181, 622–629.

    Article  PubMed  CAS  Google Scholar 

  • Brown D. A. and Rose J. K. (1992) Sorting of GPI-anchored proteins to glycolipids-enriched membrane subdomains during transport to the apical cell surface. Cell 68, 533–544.

    Article  PubMed  CAS  Google Scholar 

  • Brown D. A. and London E. (1998) Function of lipid rafts in biological membranes. Ann. Rev. Cell. Devel. Biol. 14, 111–136.

    Article  CAS  Google Scholar 

  • Brown D. A. and London E. (2000) Structure and function of sphingolipid-and cholesterol-rich membrane rafts. J. Biol. Chem. 275, 17,221–17,224.

    Article  PubMed  CAS  Google Scholar 

  • Budowski P. (1988) Omega-3-Fatty acids in health and disease. World Rev. Nutr. Diet 57, 214–274.

    PubMed  CAS  Google Scholar 

  • Edidin M. (2003) The state of lipid rafts: from model membranes to cells. Annu. Rev. Biophys. Biomolec. Struct. 32, 257–283.

    Article  CAS  Google Scholar 

  • Freedman S. D., Katz M. H., Parker E. M., Laposata M., Urman M. Y., and Alvarez J. G. (1999) A membrane lipid imbalance plays a role in the phenotypic expression of cystic fibrosis in cftr(−/−) mice. Proc. Natl. Acad. Sci. USA 96, 13,995–14,000.

    Article  PubMed  CAS  Google Scholar 

  • Furuchi T. and Anderson R. G. W. (1998) Cholesterol depletion of caveoli. J. Biol. Chem. 273, 21,099–21,104.

    Article  PubMed  CAS  Google Scholar 

  • Ghosh J. and Myers C. E. (1998) Inhibition of arachidonate 5-lipoxygenase triggers massive apoptosis in human prostate cancer cells. Proc. Natl. Acad. Sci. USA 95, 13,182–13,187.

    Article  PubMed  CAS  Google Scholar 

  • Hakomori S. and Igarashi Y. (1993) Gangliosides and glycosphingolipids as modulators of cell growth, adhesion, and transmembrane signaling. Adv. Lipid Res. 25, 147–162.

    PubMed  CAS  Google Scholar 

  • Hakomori S. and Igarashi Y. (1995) Functional role of glycosphingolipids in cell recognition and signaling. J. Biochem. (Tokyo) 118, 1091–1103.

    CAS  Google Scholar 

  • Hakomori S., Yamamura S., and Handa A. K. (1998) Signal transduction through glyco(sphingo)lipids. Introduction and recent studies on glyco(sphingo)lipid-enriched microdomains. Ann. NY Acad. Sci. 845, 1–10.

    Article  PubMed  CAS  Google Scholar 

  • Halliwell B. and Gutteridge J. M. (1984) Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem. J. 219, 1–14.

    PubMed  CAS  Google Scholar 

  • Harbige L. S. (1998) Dietary ω6 and ω3 fatty acids in immunity and autoimmune disease. Proc. Nutr. Soc. 57, 555–562.

    Article  PubMed  CAS  Google Scholar 

  • Hering H., Lin C. C., and Sheng M. (2003) Lipid rafts in the maintenance of synapses, dendritic spines, and surface AMPA receptor stability. J. Neurosci. 23, 3262–3271.

    PubMed  CAS  Google Scholar 

  • Iwabuchi K., Handa K., and Hakomori S. (2000) Separation of glycosphingolipid-enriched microdomains from caveolar membrane characterized by presence of caveolin. Methods Enzymol. 312, 488–494.

    Article  PubMed  CAS  Google Scholar 

  • Koudinov A. R. and Koudinova N. V. (2001) Essential role for cholesterol in synaptic plasticity and neuronal degeneration. FASEB J. 15, 1858–1860.

    PubMed  CAS  Google Scholar 

  • Ledeen R. W., Wu G., Lu Z. H., Kozireski-Chuback D., and Fang Y. (1998) The role of GM1 and other gangliosides in neuronal differentiation. Overview and new finding. Ann. NY Acad. Sci. 845, 161–175.

    Article  PubMed  CAS  Google Scholar 

  • Ma L., Huang Y. Z., Pitcher G. M., Valtschanoff J. G., Ma Y. H., Feng L. Y., et al. (2003) Ligand-dependent recruitment of the ErbB4 signaling complex into neuronal lipid rafts. J. Neurosci. 23, 3164–3175.

    PubMed  CAS  Google Scholar 

  • Mauch D. H., Nagler K., Schumacher S., Goritz C., Muller E. C., Otto A., et al. (2001) CNS synaptogenesis promoted by glia-derived cholesterol. Science 294, 1354–1357.

    Article  PubMed  CAS  Google Scholar 

  • Martinez M. and Vazquez E. (1998) MRI evidence that docosahexaenoic acid ethyl ester improves myelination in generalized peroxisomal disorders. Neurology 51, 26–32.

    PubMed  CAS  Google Scholar 

  • Melchior D. L. (1986) Lipid domains in fluid membranes: A quick-freeze differential scanning calorimetry study. Science 234, 1577–1580.

    Article  PubMed  CAS  Google Scholar 

  • Mouritsen O. G. and Jorgensen K. (1998) A new look at lipid-membrane structure in relation to drug research. Pharmac. Res. 15, 1507–1519.

    Article  CAS  Google Scholar 

  • Phylactos A., Harbige L. S., and Crawford M. A. (1994) Essential fatty acids alter the activity of manganese-superoxide dismutase in rat heart. Lipids 29, 111–115.

    Article  PubMed  CAS  Google Scholar 

  • Pike L. (2003) Lipid rafts: bringing order to chaos. J. Lipid Res. 44, 655–667.

    Article  PubMed  CAS  Google Scholar 

  • Pric P. T., Nelson C. M., and Clarke S. D. (2000) Omega-3 polyunsaturated fatty acid regulation of gene expression. Curr. Opin. Lipidol. 11, 3–7.

    Article  Google Scholar 

  • Rietved A. and Simons K. (1998) The differential miscibility of lipids as the basis for the formation of functional membrane rafts. Biochim. Biophys. Acta 1376, 467–479.

    Google Scholar 

  • Rodgers W. and Rose J. K. (1996) Exclusion of CD45 inhibits activity of p56lck associated with glycolipid-enriched membrane domains. J. Cell Biol. 135, 1515–1523.

    Article  PubMed  CAS  Google Scholar 

  • Salem N. Jr. (1989) Omega-3 fatty acids: molecular and biochemical aspect. In New Protective Roles of Selected Nutrients in Human Nutrition. Spiller G. and Scala J., eds., Alan R. Liss, NY, pp. 109–228.

    Google Scholar 

  • Seelig J. and Seelig A. (1980) A lipid conformation in model membranes and biological membranes. Quart. Rev. Biophys. 13, 19–61.

    Article  CAS  Google Scholar 

  • Sheets E. D., Lee G. M., Simson R., and Jacobsen K. (1997) Transient confinement of a glycosylphosphatidylinositol-anchored protein in the plasma membrane. Biochemistry 34, 12,449–12,459.

    Article  Google Scholar 

  • Singer S. J. and Nicolson G. L. (1972) The fluid mosaic model of cell membranes. Science 175, 720–731.

    Article  PubMed  CAS  Google Scholar 

  • Simons K. and van Meer G. (1988) Lipid sorting in epithelial cells. Biochemistry 27, 6197–6202.

    Article  PubMed  CAS  Google Scholar 

  • Simons K. and Ikonnen E. (1997) Functional rafts in cell membranes. Nature 389, 569–572.

    Article  CAS  Google Scholar 

  • Simons K. and Toomre D. (2000) Lipid rafts and signal transduction. Nat. Rev. Mol. Cell Biol. 1, 31–41.

    Article  PubMed  CAS  Google Scholar 

  • Simons M., Keller P., De Strooper B., Beyreuther K., Dotti C. G., and Simons K. (1998) Cholesterol depletion inhibits the generation of beta-amyloid in hippocampal neurons. Proc. Natl. Acad. Sci. USA 95, 6460–6464.

    Article  PubMed  CAS  Google Scholar 

  • Smart E. J., Graf G. A., McNiven M. A., Sessa W. C., Engelman J. A., Scherer P. E., et al. (1999) Caveolins, liquid-ordered domains, and signal transduction. Mol. Cell. Biol. 19, 7289–7304.

    PubMed  CAS  Google Scholar 

  • Stulnig T. M., Huber J., Leitinger N., Imre E. M., Angelisova P., Nowotny P., et al. (2001) Polyunsaturated eicosapentaenoic acid displaces proteins from membrane rafts by altering raft lipid composition. J. Biol. Chem. 276, 37,335–37,340.

    Article  PubMed  CAS  Google Scholar 

  • Verkleij A. J. and Post J. A. (2000) Membrane phospholipid asymmetry and signal transduction. J. Membr. Biol. 178, 1–10.

    Article  PubMed  CAS  Google Scholar 

  • Yavin E., Brand A., and Green P. (2002) Docosahexaenoic acid abundance in the brain: A biodevice to combat oxidative stress. Nutr. Neurosci. 5, 149–157.

    Article  PubMed  CAS  Google Scholar 

  • Yeagle P. L. (1985) Cholesterol and the cell membrane. Biochim. Biophys. Acta 822, 267–287.

    PubMed  CAS  Google Scholar 

  • Yeagle P. L. (1993) The Membrane of Cells. Academic, San Diego, CA, pp. 69–165.

    Google Scholar 

  • Zwaal R. F. A. and Schroit A. J. (1997) Pathophysiological implications of membrane phospholipid asymmetry in blood cells. Blood 89, 1121–1132.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, Baltimore, MD

    Ephraim Yavin

  2. Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel

    Ephraim Yavin

  3. Department of Pediatrics, Georgetown University, Washington, DC

    Annette Brand

Authors
  1. Ephraim Yavin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Annette Brand
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, Baltimore, MD

    Mark P. Mattson

  2. Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD

    Mark P. Mattson

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Yavin, E., Brand, A. (2005). From Intramolecular Asymmetries to Raft Assemblies. In: Mattson, M.P. (eds) Membrane Microdomain Signaling. Humana Press. https://doi.org/10.1385/1-59259-803-X:001

Download citation

Publish with us

Policies and ethics

Search

Navigation