A critical role of lipid rafts in the organization of a key FcγRIIa-mediated signaling pathway in human platelets

 

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Summary

The involvement of platelet FcγRIIa in heparin-associated thrombocytopenia (HIT) is now well established. However, the precise sequence of molecular events initiated by FcγRIIa cross-linking in platelets remains partly characterized. We investigated here the role of lipid rafts in the spatio-temporal organization of the FcγRIIa-dependent signaling events. Upon cross-linking, FcγRIIa relocated in rafts where the kinase Lyn and the adapter LAT were among the major phosphotyrosyl proteins. Upon stimulation by HIT sera, the second messenger phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P₃) accumulated in rafts in a P₂Y₁₂ adenosine diphosphate (ADP) recep- tor-dependent manner. PtdIns(3,4,5)P₃ was then essential to specifically recruit phospholipase Cγ2 (PLCγ2) to these membrane microdomains. Controlled disruption of rafts by methyl γ-cyclodextrin reversibly abolished PtdIns(3,4,5)P₃ production, PLC activation and platelet responses induced by FcγRIIa cross-linking without affecting the tyrosine phosphorylation events. This work demonstrates that platelet rafts are essential for the integration of a key signaling complex leading to the rapid production of PtdIns(3,4,5)P₃ and in turn PLCγ2 activation during HIT.

• References

• 1 Canobbio I, Bertoni A, Lova P, Paganini S, Hirsch E, Sinigaglia F, Balduini C, Torti M. Platelet activation by von Willebrand factor requires coordinated signaling through thromboxane A2 and Fc gamma IIA receptor. J Biol Chem 2001; 276: 26022-9.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 2 Reilly MP, Taylor SM, Hartman NK, Arepally GM, Sachais BS, Cines DB, Poncz M, McKenzie SE. Heparin-induced thrombocytopenia/thrombosis in a transgenic mouse model requires human platelet factor 4 and platelet activation through FcgammaRIIA. Blood 2001; 98: 2442-7.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 3 McKenzie SE, Taylor SM, Malladi P, Yuhan H, Cassel DL, Chien P, Schwartz E, Schreiber AD, Surrey S, Reilly MP. The role of the human Fc receptor Fc gamma RIIA in the immune clearance of platelets: a transgenic mouse model. J Immunol 1999; 162: 4311-8.
  MissingFormLabel

  PubMedSearch in Google Scholar
• 4 Anderson CL, Chacko GW, Osborne JM, Brandt JT. The Fc receptor for immunoglobulin G (Fc gamma RII) on human platelets. Semin Thromb Hemost 1995; 21: 1-9.
  MissingFormLabel

  Thieme ConnectPubMedSearch in Google Scholar
• 5 Warkentin TE. Heparin-induced thrombocytopenia: a ten-year retrospective. Annu Rev Med 1999; 50: 129-47.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 6 Polgar J, Eichler P, Greinacher A, Clemetson KJ. Adenosine diphosphate (ADP) and ADP receptor play a major role in platelet activation/aggregation induced by sera from heparin-induced thrombocytopenia patients. Blood 1999; 91: 549-54.
  MissingFormLabel

  PubMedSearch in Google Scholar
• 7 Herault JP, Lale A, Savi P, Pflieger AM, Herbert JM. In vitro inhibition of heparin- induced platelet aggregation in plasma from patients with HIT by SR 121566, a newly developed Gp IIb/IIIa antagonist. Blood Coagul Fibrinolysis 1997; 8: 206-7.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 8 Gratacap MP, Hérault JP, Viala C, Ragab A, Savi P, Herbert JM, Chap H, Plantavid M, Payrastre B. FcgammaRIIA requires a Gi-dependent pathway for an efficient stimulation of phosphoinositide 3-kinase, calcium mobilization, and platelet aggregation. Blood 2000; 96: 3439-46.
  MissingFormLabel

  PubMedSearch in Google Scholar
• 9 Chacko GW, Duchemin AM, Coggeshall KM, Osborne JM, Brandt JT, Anderson CL. Clustering of the platelet Fc gamma receptor induces noncovalent association with the tyrosine kinase p72syk. J Biol Chem 1994; 269: 32435-40.
  MissingFormLabel

  PubMedSearch in Google Scholar
• 10 Yanaga F, Poole A, Asselin J, Blake R, Schieven GL, Clark EA, Law CL, Watson SP. Syk interacts with tyrosine-phosphory-lated proteins in human platelets activated by collagen and cross-linking of the Fc gamma-IIA receptor. Biochem J 1995; 311: 471-8.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 11 Gratacap MP, Payrastre B, Viala C, Mauco G, Plantavid M, Chap H. Phosphatidylinositol 3,4,5-trisphosphate-dependent stimulation of phospholipase C-gamma2 is an early key event in FcgammaRIIA-mediated activation of human platelets. J Biol Chem 1998; 273: 24314-21.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 12 Huang MM, Indik Z, Brass LF, Hoxie JA, Schreiber AD, Brugge JS. Activation of Fc gamma RII induces tyrosine phosphorylation of multiple proteins including Fc gamma RII. J Biol Chem 1992; 267: 5467-73.
  MissingFormLabel

  PubMedSearch in Google Scholar
• 13 Ibarrola I, Vossebeld PJ, Homburg CH, Thelen M, Roos D, Verhoeven AJ. Influence of tyrosine phosphorylation on protein interaction with FcgammaRIIa. Biochim Biophys Acta 1997; 1357: 348-58.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 14 Chacko GW, Brandt JT, Coggeshall KM, Anderson CL. Phosphoinositide 3-kinase and p72syk noncovalently associate with the low affinity Fc gamma receptor on human platelets through an immunoreceptor tyrosine-based activation motif. Reconstitution with synthetic phosphopeptides. J Biol Chem 1996; 271: 10775-81.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 15 Pasquet JM, Bobe R, Gross B, Gratacap MP, Tomlinson MG, Payrastre B, Watson SP. A collagen-related peptide regulates phospho-lipase Cgamma2 via phosphatidylinositol 3-kinase in human platelets. Biochem J 1999; 342: 171-7.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 16 Pasquet JM, Gross BS, Gratacap MP, Quek L, Pasquet S, Payrastre B, van Willigen G, Mount-ford JC, Watson SP. Thrombopoietin potentiates collagen receptor signaling in platelets through a phosphatidylinositol 3-kinase-dependent pathway. Blood 2000; 95: 3429-34.
  MissingFormLabel

  PubMedSearch in Google Scholar
• 17 Payrastre B, Gratacap MP, Trumel C, Missy K, Chap H, Gachet C and Plantavid M. ADP: an important cofactor of PI 3-kinase activation in human blood platelets. Haematologica 2000; 85: 32-6.
  MissingFormLabel

  PubMedSearch in Google Scholar
• 18 Simons K, Ikonen E. Functional rafts in cell membranes. Nature 1997; 387: 569-72.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 19 Simons K, Toomre D. Lipid rafts and signal transduction. Nature Reviews 2000; 1: 31-9.
  MissingFormLabel

  PubMedSearch in Google Scholar
• 20 Langlet C, Bernard AM, Drevot P, He HT. Membrane rafts and signaling by the multi-chain immune recognition receptors. Curr Opin Immunol 2000; 12: 250-5.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 21 Montixi C, Langlet C, Bernard AM, Thimonier J, Dubois C, Wurbel MA, Chauvin JP, Pierres M, He HT. Engagement of T cell receptor triggers its recruitment to low-density detergent-insoluble membrane domains. Embo J 1998; 17: 5334-48.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 22 Xavier R, Brennan T, Li Q, McCormack C, Seed B. Membrane compartmentation is required for efficient T cell activation. Immunity 1998; 8: 723-32.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 23 Viola A, Schroeder S, Sakakibara Y, Lanzavecchia A. T lymphocyte costimulation mediated by reorganization of membrane micro-domains. Science 1999; 283: 680-2.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 24 Field KA, Holowka D, Baird B. Fc epsilon RI-mediated recruitment of p53/56lyn to detergent-resistant membrane domains accompanies cellular signaling. Proc Natl Acad Sci USA 1995; 92: 9201-5.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 25 Field KA, Holowka D, Baird B. Compartmentalized activation of the high affinity immunoglobulin E receptor within membrane domains. J Biol Chem 1997; 272: 4276-80.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 26 Sheets ED, Holowka D, Baird B. Critical role for cholesterol in Lyn-mediated tyrosine phosphorylation of FcepsilonRI and their association with detergent-resistant membranes. J Cell Biol 1999; 145: 877-87.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 27 Pasquet JM, Gross B, Quek L, Asazuma N, Zhang W, Sommers CL, Schweighoffer E, Tybulewicz V, Judd B, Lee JR, Koretzky G, Love PE, Samelson LE, Watson SP. LAT is required for tyrosine phosphorylation of phospholipase cgamma2 and platelet activation by the collagen receptor GPVI. Mol Cell Biol 1999; 19: 8326-34.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 28 Zhang W, Trible RP, Samelson LE. LAT palmitoylation: its essential role in membrane microdomain targeting and tyrosine phosphorylation during T cell activation. Immunity 1998; 9: 239-46.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 29 Bodin S, Giuriato S, Ragab J, Humbel BM, Viala C, Vieu C, Chap H, Payrastre B. 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. Biochemistry 2001; 40: 15290-9.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 30 Wonerow P, Watson SP. The transmembrane adapter LAT plays a central role in immune receptor signalling. Oncogene 2001; 20: 6273-83.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 31 Locke D, Chen H, Liu Y, Liu C, Kahn ML. Lipid rafts orchestrate signaling by the platelet receptor glycoprotein VI. J Biol Chem 2002; 277: 18801-9.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 32 Wonerow P, Obergfell A, Wilde JI, Bobe R, Asazuma N, Brdicka T, Leo A, Schraven B, Horejsi V, Shattil SJ, Watson SP. Differential role of glycolipid-enriched membrane domains in glycoprotein VI- and integrin-mediated phospholipase C 2 regulation in platelets. Biochem J 2002; 364: 755-65.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 33 Dorahy DJ, Burns GF. Biochemical isolation of a membrane microdomain from resting platelets highly enriched in the plasma membrane glycoprotein CD36. Biochem J 1998; 333: 373-9.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 34 Pike LJ, Casey L. Localization and turnover of phosphatidylinositol 4,5-bisphosphate in aveolin-enriched membrane domains. J Biol Chem 1996; 271: 26453-6.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 35 Liu Y, Casey L, Pike LJ. Compartment-alization of phosphatidylinositol 4,5-bisphosphate in low-density membrane domains in the absence of caveolin. Biochem Biophys Res Commun 1998; 245: 684-90.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 36 Bligh EG, Dyer WJ. A rapid method of lipid extraction and purification. Can J Biochem Phys 1959; 37: 911-7.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 37 Vieu C, Jaspard B, Barbaras R, Manent J, Chap H, Perret B, Collet X. Identification and quantification of diacylglycerols in HDL and accessibility to lipase. J Lipid Res 1996; 37: 1153-61.
  MissingFormLabel

  PubMedSearch in Google Scholar
• 38 Payrastre B, Missy K, Giuriato S, Bodin S, Plantavid M, Gratacap M. Phosphoinositides: key players in cell signalling, in time and space. Cell Signal 2001; 13: 377-87.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 39 Huang R, Kucera GL, Rittenhouse SE. Elevated cytosolic Ca2+ activates phospholipase D in human platelets. J Biol Chem 1991; 266: 1652-5.
  MissingFormLabel

  PubMedSearch in Google Scholar
• 40 Kabouridis PS, Janzen J, Magee AL, Ley SC. Cholesterol depletion disrupts lipid rafts and modulates the activity of multiple signaling pathways in T lymphocytes. Eur J Immunol 2000; 30: 954-63.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 41 Barabe F, Rollet-Labelle E, Gilbert C, Fernandes MJG, Naccache SM, Naccache PH. Early events in the activation of FcgRIIA in human neutrophils: Stimulated Insolubilization, Translocation to Detergent-resistant domains, and Degradation of Fc RIIA. J Immunol 2000; 168: 4042-9.
  MissingFormLabel

  PubMedSearch in Google Scholar
• 42 Watson SP, Gibbins J. Collagen receptor signalling in platelets: extending the role of the ITAM. Immunol Today 1998; 19: 260-4.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 43 Katsumata O, Hara-Yokoyama M, Sautes-Fridman C, Nagatsuka Y, Katada T, Hirabayashi Y, Shimizu K, Fujita-Yoshigaki J, Sugiya H, Furuyama S. Association of FcgammaRII with low-density detergent-resistant membranes is important for cross-linking-dependent initiation of the tyrosine phosphorylation pathway and superoxide generation. J Immunol 2001; 167: 5814-23.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 44 Saci A, Pain S, Rendu F, Bachelot-Loza C. Fc receptor-mediated platelet activation is dependent on phosphatidylinositol 3-kinase activation and involves p120(Cbl). J Biol Chem 1999; 274: 1898-904.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 45 Todderud G, Wahl MI, Rhee SG, Carpenter G. Stimulation of phospholipase C-gamma 1 membrane association by epidermal growth factor. Science 1990; 249: 296-8.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 46 Li S, Couet J, Lisanti MP. Src tyrosine kinases, Galpha subunits, and H-Ras share a common membrane-anchored scaffolding protein, caveolin. Caveolin binding negatively regulates the auto-activation of Src tyrosine kinases. J Biol Chem 1996; 271: 29182-90.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 47 Smart EJ, Ying YS, Mineo C, Anderson RG. A detergent-free method for purifying caveolae membrane from tissue culture cells. Proc Natl Acad Sci USA 1995; 92: 10104-8.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 48 Oh P, Schnitzer JE. Segregation of hetero-trimeric G proteins in cell surface micro-domains. G(q) binds caveolin to concentrate in caveolae, whereas G(i) and G(s) target lipid rafts by default. Mol Biol Cell 2001; 12: 685-98.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 49 Chang WJ, Ying YS, Rothberg KG, Hooper NM, Turner AJ, Gambliel HA, De Gunzburg J, Mumby SM, Gilman AG, Anderson RG. Purification and characterization of smooth muscle cell caveolae. J Cell Biol 1994; 126: 127-38.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 50 Schnitzer JE, Liu J, Oh P. Endothelial caveolae have the molecular transport machinery for vesicle budding, docking, and fusion including VAMP, NSF, SNAP, annexins, and GTPases. J Biol Chem 1995; 270: 14399-404.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 51 Maier U, Babich A, Nurnberg B. Roles of non-catalytic subunits in gbetagamma-induced activation of class I phosphoinositide 3-kinase isoforms beta and gamma. J Biol Chem 1999; 274: 29311-7.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 52 Kurosu H, Maehama T, Okada T, Yamamoto T, Hoshino S, Fukui Y, Ui M, Hazeki O, Katada T. Heterodimeric phosphoinositide 3-kinase consisting of p85 and p110beta is synergistically activated by the betagamma subunits of G proteins and phosphotyrosyl peptide. J Biol Chem 1997; 272: 24252-6.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 53 Kwiatkowska K, Sobota A. The clustered Fcgamma receptor II is recruited to Lyn-containing membrane domains and undergoes phosphorylation in a cholesterol-dependent manner. Eur J Immunol 2001; 31: 989-98.
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar