Platelet tetraspanin complexes and their association with lipid rafts

Summary

Tetraspanins are a superfamily of integral membrane proteins that facilitate the organization of membrane and intracellular signaling molecules into dynamic signaling microdomains, tetraspaninenriched microdomains (TEMs). Four tetraspanin family members have been identified in platelets: CD9, CD151 and TSSC6, which are constitutively associated with αIIb3, and CD63, which is present on granule membranes in resting platelets and associates with αIIbβ3-CD9 following platelet activation. CD63 and CD9 associate with a type II phosphatidylinositol 4-kinase, PI4K55, in both resting and activated platelets. Immunoelectron microscopic studies showed co-localization of CD63 and PI4K55 on internal membranes of resting platelets and on the filopodia of thrombin-activated platelets. Because TEMs in malignant cell lines appear to be distinct from prototypic lipid rafts, this study examined whether CD63-PI4K55 and CD9-PI4K55 complexes were resident in platelet-lipid rafts, or formed distinct microdomains. CD63, CD9 and PI4K55 were recovered from low-density membrane fractions (LDMFs) of sucrose gradients following platelet lysis in Brij 35, but unlike lipidraft proteins were not insoluble in Triton X-100, being absent from LDMFs of platelets lysed with Triton. In cubation of platelets with methyl-β-cyclodextrin, to deplete cholesterol and disrupt lipid rafts, shifted the complexes to higher density sucrose gradient fractions, but did not disrupt the tetraspanin-PI4K55 complexes. These results demonstrate that tetraspanin complexes in platelets form cholesterol-associated microdomains that are distinct from lipid rafts. It is probable thatTEMs and lipid rafts associate under certain conditions, resulting in the close proximity of distinct sets of signaling molecules, facilitating signal transduction.

Keywords

Blood platelets - tetraspanin - CD63 - phosphatidylinositol 4-kinase - lipid raft

• References

• 1 Hemler ME. Tetraspanin functions and associated microdomains. Nature Rev Mol Cell Biol 2005; 6: 801-811.
• 2 Hemler ME. Tetraspanin proteins mediate cellular penetration, invasion, and fusion events and define a novel type of membrane microdomain. Annu Rev Cell Dev Biol 2003; 19: 397-422.
• 3 Levy S, Shoham T. The tetraspanin web modulates immuno-signalling complexes. Nature Rev Immunol 2005; 5: 136-148.
• 4 Boucheix C, Rubenstein E. Tetraspanins. Cell Mol Life Sci 2001; 58: 1189-1205.
• 5 Penas PF. et al. Tetraspanins are localized at motility- related structures and involved in normal human keratinocyte wound healing migration. J Invest Dermatol 2000; 114: 1126-1135.
• 6 Woods A, Couchman JR. Integrin modulation by lateral association. J Biol Chem 2000; 275: 24233-24236.
• 7 Brown DA, London E. Structure and function of sphingolipid- and cholesterol-rich membrane rafts. J Biol Chem 2000; 275: 17221-17224.
• 8 Claas C. et al. Evaluation of prototype TM4SF protein complexes and their relation to lipid rafts. J Biol Chem 2001; 276: 7974-7984.
• 9 Yashiro-Ohtani Y. et al. Non-CD28 costimulatory molecules present in T cell rafts induce T cell costimulation by enhancing the association of TCR with rafts. J Immunol 2000; 164: 1251-1259.
• 10 Charrin S. et al. Multiple levels of interactions within the tetraspanin web. Biochem Biophys Res Commun 2003; 304: 107-112.
• 11 Foster LJ. et al. Unbiased quantitative proteomics of lipid rafts reveals high specificity for signaling factors. Proc Nat Acad Sci USA 2003; 100: 5813-5818.
• 12 Israels SJ. et al. CD63 associates with the αIIbβ3 integrin-CD9 complex on the surface of activated platelets. Thromb Haemost 2001; 85: 134-141.
• 13 Indig FE. et al. Analysis of the tetraspanin CD9-integrin αIIbβ3 (GPIIb-IIIa) complex in platelet membranes and transfected cells. Biochem J 1997; 327: 291-298.
• 14 Brisson C. et al. Co-localization of CD9 and GPIIb- IIIa(αIIbβ3 integrin) on activated platelet pseudopods and α-granule membranes. Histochem J 1997; 29: 153-165.
• 15 Fitter S. et al. Transmembrane 4 superfamily protein CD151 (PETA-3) associates with β1 and αIIbβ3 integrins in haematopoietic cell lines and modulates cell-cell adhesion. Biochem J 1999; 338: 61-70.
• 16 Goschnick MW. et al. Impaired “outside-in” integrin αIIbβ3 signaling and thrombus stability in TSSC6-deficient mice. Blood 2006; 108: 1911-1918.
• 17 Lau L-M. et al. The tetraspanin superfamily member CD151 regulates ouside-in integrin αIIbβ3 signaling and platelet function. Blood 2004; 104: 2368-2375.
• 18 Israels SJ. et al. CD63 modulates spreading and tyrosine phosphorylation of platelets on immobilized fibrinogen. Thromb Haemost 2005; 93: 311-318.
• 19 Berdistchevski F. Complexes of tetraspanins with integrins: more than meets the eye. J Cell Sci 2001; 114: 4143-4151.
• 20 Gehrmann R, Heilmeyer Jr. LMG. Phosphatidylinositol 4-kinases. Eur J Biochem 1998; 253: 357-370.
• 21 Bodin S. et al. Lipid rafts are critical membrane domains in blood platelet activation processes. Biochim Biophys Acta 2003; 1610: 247-257.
• 22 Wonerow P. et al. Differential role for glycolipidenriched membrane domains in glycoprotein VI- and integrin-mediated phospholipase Cγ2 regulation in platelets. Biochem J 2002; 364: 755-765.
• 23 Shrimpton CN. et al. Localization of the adhesion receptor glycoprotein Ib-IX-V complex to lipid rafts is required for platelet adhesion and activation. J Exp Med 2002; 196: 1057-1066.
• 24 Ezumi Y. at al. Constitutive and functional association of the platelet collagen receptor glycoprotein VIFc receptor gamma-chain complex with membrane rafts. Blood 2002; 99: 3250-3255.
• 25 Bodin S. et al. Production of phosphatidylinositol 3,4,5-trisphosphate and phosphatidic acid in platelet rafts: evidence for a critical role of cholesterol-enriched domains in human platelet activation. Biochem 2001; 40: 15290-15299.
• 26 Heijnen HFG. et al. Concentration of rafts in platelet filopodia correlates with recruitment of c-Src and CD63 to these domains. J Thromb Haemost 2003; 1: 1161-1173.
• 27 Van Lier M. et al. Adhesive surface determines raft composition in platelets adhered under flow. Thromb Haemost 2005; 25: 14-25.
• 28 Bodin S. et al. Integrin-dependent interaction of lipid rafts with the actin cytoskeleton in activated human platelets. J Cell Sci 2005; 118: 759-769.
• 29 Gerrard JM. et al. Identification of a platelet dense granule membrane protein which is deficient in a patient with the Hermansky-Pudlak syndrome. Blood 1991; 77: 101-112.
• 30 Nishibori M. et al. The protein CD63 is in platelet dense granules, is deficient in a patient with Hermansky- Pudlak syndrome, and appears identical to granulophysin. J Clin Invest 1993; 91: 1775-1782.
• 31 Endemann GC. et al. A monoclonal antibody distinguishes two types of phosphatidylinositol 4-kinase. Biochem J 1991; 273: 63-66.
• 32 McNicol A. Platelet preparation and estimation of functional responses. In: Platelets: A Practical Approach. Oxford:: Oxford University Press; 1996: 1-26.
• 33 Indig FE. et al. Analysis of the tetraspanin CD9-integrin αIIbβ3 (GPIIb-IIIa) complex in platelet membranes and transfected cells. Biochem J 1997; 327: 291-298.
• 34 McNicol A. et al. Vanadate activates platelets by enhancing arachidonic acid release. Blood 1993; 81: 2329-2338.
• 35 Gousett K. et al. Evidence for a physiological role for membrane rafts in human platelets. J Cell Phsyiol 2002; 190: 117-128.
• 36 McNicol A. et al. Incorporation of MAP kinases into the platelet cytoskeleton. Thromb Res 2001; 103: 25-34.
• 37 Charrin S. et al. A physical and functional link between cholesterol and tetraspanins. Eur J Immunol 2003; 33: 2479-2489.
• 38 Israels SJ. et al. Platelet dense granule membranes contain both granulophysin and P-selectin(GMP-140). Blood 1992; 80: 143-152.
• 39 Berditchevski F. et al. A novel link between integrins, transmembrane-4 superfamily proteins (CD63 and CD81), and phosphatidylinositol 4-kinase. J Biol Chem 1997; 272: 2595-2598.
• 40 Yauch L, Hemler ME. Specific interactions among transmembrane 4 superfamily (TM4SF) proteins and phosphoinositide 4-kinase. Biochem J 2000; 351: 629-637.
• 41 Kaufmann-Zeh A. et al. Requirement for phosphatidylinositol transfer protein in epidermal growth factor signalling. Science 1995; 268: 1188-1190.
• 42 Pertile P, Cantley LC. Type 2 phosphatidylinositol 4-kinase is recruited to CD4 in response to CD4 crosslinking. Biochim Biophys Acta 1995; 1248: 129-134.
• 43 Heilmeyer Jr LMG. et al. Mammalian phosphatidylinositol 4-kinases. IUBMB Life 2003; 55: 59-65.
• 44 Wonerow P. et al. A critical role for phospholipase Cγ2 in αIIbβ3-mediated platelet spreading. J Biol Chem 2003; 278: 37520-37529.
• 45 Dorahy DJ. et al. Biochemical isolation of a membrane microdomain from resting platelets highly enriched in the plasma membrane glycoprotein CD36. Biochem J 1996; 319: 67-72.
• 46 Dorahy DJ, Burns GF. Active Lyn protein tyrosine kinase is selectively enriched within membrane microdomains of resting platelets. Biochem J 1998; 333: 373-379.
• 47 Le Naour F. et al. Membrane microdomains and proteomincs: lessons from tetraspanin microdomains and comparison with lipid rafts. Proteomics 2006; 6: 6447-6454.
• 48 Nydegger S. et al. Mapping of tetraspanin-enriched microdomains that can function as gateways for HIV-1. J Cell Biol 2006; 173: 795-807.
• 49 Schuck S. et al. Resistance of cell membranes to different detergents. Proc Nat Acad Sci USA 2003; 100: 5795-5800.
• 50 Chamberlain LH. Detergents as tools for the purification and classification of lipid rafts. FEBS Letts 2004; 559: 1-5.
• 51 Locke D. et al. Lipid rafts orchestrate signaling by the platelet receptor glycoprotein VI. J Biol Chem 2002; 277: 18801-18809.
• 52 Abitorabi MA. et al. Presentation of integrins on leukocyte microvilli: a role for extracellular domains in determining membrane localization. J Cell Biol 1997; 139: 563-571.
• 53 Suguira T, Berditchevski F. Function of α3β1-tetraspanin protein complexes in tumor cell invasion. Evidence for the role of the complexes in production of matrix metalloproteinase 2. J Cell Biol 1999; 146: 1375-1389.