Advertisement

Signal Transduction Via GPI-Anchored Membrane Proteins

  • Peter J. Robinson
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 419)

Abstract

Eukaryotic cells carry upon their cell surfaces a number of proteins which are anchored in the membrane via glycosylphosphatidylinositol (GPI) membrane anchors1 These proteins are attached to the cell membrane by hydrophobic attraction of the phospholipid tails of the GPI-anchor with lipids in the outer face of the plasma membrane bilayer. Consequently, they neither span the cell membrane nor do they interact directly with intracellular components. During intracellular transport, GPI anchors recruit specialized lipids and glycolipids(2,3,4). Acquisition of these lipids renders GPI-anchored proteins insoluble in a number of non-ionic detergents, and enables their enrichment in cell lysates by density-gradient centrifugation. These associated lipids, which include sphingomyelin and cholesterol, may alter the cell-surface distribution of GPI-linked molecules relative to their non-GPI-linked counterparts, and this is currently the subject of intensive study(5). These GPI-rich detergent-insoluble complexes also contain a number of other proteins which are not GPI-linked, and it is thought that these other molecules may play a key role in the functional properties of GPI anchors. It was shown using photobleaching recovery (FRAP) or single particle tracking (SPT) techniques(6) that GPI-linked molecules are not freely mobile in the cell membrane, an expected finding for a molecule which is associated only with the outer lipid leaflet of the plasma membrane. This finding implies that the mobility of Thy-1 is influenced by its association with immobile components of the membrane, and thus, indirectly, with the cytoskeleton. These observations implicate transmembrane molecules in the interactions of GPI-linked molecules with cytoplasmic and cytoskeletal components.

Keywords

Phorbol Myristate Acetate Single Particle Tracking Royal Postgraduate Medical School Immobile Component Detergent Insolubility 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Ferguson, M.A. and Williams, A.F. (1988) Cell-surface anchoring of proteins via glycosyl-phosphatidylinositol structures. Annu.Rev.Biochem. 57:285–320PubMedCrossRefGoogle Scholar
  2. 2.
    Hanada, K., Nishijima, M., Akamatsu, Y., and Pagano, R.E. (1995) Both sphingolipids and cholesterol participate in the detergent insolubility of alkaline phosphatase, a glycosylphosphatidylinositol-anchored protein, in mammalian membranes. J.Biol.Chem. 270:6254–6260PubMedCrossRefGoogle Scholar
  3. 3.
    Brown, D.A. and Rose, J.K. (1992) Sorting of GPI-anchored proteins to glycolipid-enriched membrane sub-domains during transport to the apical cell surface. Cell 68:533–544PubMedCrossRefGoogle Scholar
  4. 4.
    Brown, D.A. (1992) Interactions between GPI-anchored membrane proteins and membrane lipids. Trends in Cell Biology 2:338–343PubMedCrossRefGoogle Scholar
  5. 5.
    Mayor, S. and Maxfield, F.R. (1995) Insolubility and redistribution of GPI-anchored proteins at the cell surface after detergent treatment. Mol.Cell Biol. 6:929–944Google Scholar
  6. 6.
    Edidin, M., Kuo, S.C. and Sheetz, M.P. (1991) Lateral movement of membrane glycoproteins restricted by dynamic cytoplasmic barriers. Science 254:1379–1382PubMedCrossRefGoogle Scholar
  7. 7.
    Robinson, P.J. Phosphatidylinositol membrane anchors and T-cell activation. (1991) Immunol.Today 12:35–41PubMedCrossRefGoogle Scholar
  8. 8.
    Kroczek, R.A., Gunter, K.C., Germain, R.N., and Shevach, E.M.(1986) Thy-1 functions as a signal transduction molecule in T lymphocytes and transfected B cells. Nature 322:181–184PubMedCrossRefGoogle Scholar
  9. 9.
    Barboni, E., Gormley, A.M., Pliego Rivero, F.B., Vidal, M., and Morris, R.J. (1991) Activation of T lymphocytes by cross-linking of glycophospholipid-anchored Thy-1 mobilizes separate pools of intracellular second messengers to those induced by the antigen-receptor/CD3 complex. Immunology 72:457–463PubMedGoogle Scholar
  10. 10.
    Mason, J.C., Yarwood, H., Tarnok, A., Sugars, K., Harrison, A.A., Robinson, P.J., and Haskard, D.O.(1996) Human Thy-1 is cytokine-inducible on vascular endothelial cells and is a signalling molecule regulated by protein kinase C. J.Immunol. In pressGoogle Scholar
  11. 11.
    Shenoy Scaria, A.M., Kwong, J., Fujita, T., Olszowy, M.W., Shaw, A.S., and Lublin, D.M.(1992) Signal transduction through decay-accelerating factor. Interaction of glycosyl-phosphatidylinositol anchor and protein tyrosine kinases p561ck and p59fyn. J.Immunol. 149:3535–3541.PubMedGoogle Scholar
  12. 12.
    Pingel, J.T. and Thomas, M.L.(1989) Evidence that the leukocyte-common antigen is required for antigeninduced T lymphocyte proliferation. Cell 58:1055–1065PubMedCrossRefGoogle Scholar
  13. 13.
    Pingel, J.T., Cahir McFarland, E.D., and Thomas, M.L.(1994) Activation of CD45-deficient T cell clones by lectin mitogens but not anti-Thy-1. Int.Immunol. 6:169–178PubMedCrossRefGoogle Scholar
  14. 14.
    Volarevic, S., Burns, C.M., Sussman, J.J., and Ashwell, J.D.(1990) Intimate association of Thy-1 and the T-cell antigen receptor with the CD45 tyrosine phosphatase. Proc.Natl.Acad.Sci.U.S.A. 81:7085–7089CrossRefGoogle Scholar
  15. 15.
    Takeda, A. (1993) Sphingolipid-like molecule linked to CD45, a protein tyrosine phosphatase Adv.Lipid Res. 26:293–317PubMedGoogle Scholar
  16. 16.
    Parton, R.G. and Simons, K. (1995) Digging into caveolae. Science 269:1398–1399PubMedCrossRefGoogle Scholar
  17. 17.
    Mayor, S., Rothberg, K.G., and Maxfield, F.R.(1994) Sequestration of GPI-anchored proteins in caveolae triggered by cross-linking. Science 264:1948–1951PubMedCrossRefGoogle Scholar
  18. 18.
    Davis, S., Aldrich, T.H., Stahl, N., Pan, L., Taga, T., Kishimoto, T., Ip, N.Y., and Yancopoulos, G.D.(1993) LIFR and gpl30 as heterodimerizing signal transducers of the tripartite CNTF receptor. Science 260:1805–1810PubMedCrossRefGoogle Scholar
  19. 19.
    Treanor, J.J.S., Goodman, L., deSauvage, F., Stone, D.M. et.al. (1996) Characterization of a multicomponent receptor for GDNF. Nature 382: 80–83PubMedCrossRefGoogle Scholar
  20. 20.
    van den Berg, C.W., Cinek, T., Hallett, MB., Horejsi, V., and Morgan, B.P.(1995) Exogenous glycosyl-phosphatidylinositol-anchored CD59 associates with kinases in membrane clusters on U937 cells and becomes Ca2+ signalling competent. J.Cell Biol. 131:669–677PubMedCrossRefGoogle Scholar
  21. 21.
    Schofield, L. and Hackett, F.(1993) Signal transduction in host cells by a glycosylphosphatidylinositol toxin of malaria parasites. J.Exp.Med. 177:145–153PubMedCrossRefGoogle Scholar
  22. 22.
    Ilangumaran, S., Robinson, P.J. and Hoessli, D.C.(1996) Transfer of exogenous glycosylphosphatidylinositol(GPI)-linked molecules to plasma membranes Trends in Cell Biology 6: 163–167PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Peter J. Robinson
    • 1
  1. 1.Transplantation Biology Group MRC Clinical Sciences CentreRoyal Postgraduate Medical School, Hammersmith HospitalLondonEngland

Personalised recommendations