title: Lipid rafts facilitate the interaction of PECAM-1 with the glycoprotein VI-FcR gamma-chain complex in human platelets.
abstract: Glycoprotein (GP) VI, the main signaling receptor for collagen on platelets, is expressed in complex with the FcR gamma-chain. The latter contains an immunoreceptor tyrosine-based activation motif, which becomes phosphorylated, initiating a signaling cascade leading to the rapid activation and aggregation of platelets. Previous studies have shown that signaling by immunoreceptor tyrosine-based activation motif-containing receptors is counteracted by signals from receptors with immunoreceptor tyrosine-based inhibitory motifs. Here we show, by immunoprecipitation, that the GPVI-FcR gamma-chain complex associates with the immunoreceptor tyrosine-based inhibitory motif-containing receptor, PECAM-1. In platelets stimulated with collagen-related peptide (CRP-XL), tyrosine phosphorylation of PECAM-1 precedes that of the FcR gamma-chain, implying direct regulation of the former. The GPVI-FcR gamma-chain complex and PECAM-1 were present in both lipid raft and soluble fractions in human platelets; this distribution was unaltered by activation with CRP-XL. Their association occurred in lipid rafts and was lost after lipid raft depletion using methyl-beta-cyclodextrin. We propose that lipid raft clustering facilitates the interaction of PECAM-1 with the GPVI-FcR gamma-chain complex, leading to the down-regulation of the latter.
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, United Kingdom.
authors.forename: Fiona A
authors.initials: FA
authors.lastname: Lee
authors.forename: Marjolijn
authors.initials: M
authors.lastname: van Lier
authors.forename: Ingrid A M
authors.initials: IA
authors.lastname: Relou
authors.forename: Loraine
authors.initials: L
authors.lastname: Foley
authors.forename: Jan-Willem N
authors.initials: JW
authors.lastname: Akkerman
authors.forename: Harry F G
authors.initials: HF
authors.lastname: Heijnen
authors.forename: Richard W
authors.initials: RW
authors.lastname: Farndale
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D002772:Cholera Toxin / Q000737:chemistry / Q000494:pharmacology; D015536:Down-Regulation; D006801:Humans; D021962:Membrane Microdomains / Q000737:chemistry* / Q000378:metabolism; D018613:Microscopy, Confocal; D010766:Phosphorylation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000737:chemistry*; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry*; D017452:Receptors, IgG / Q000737:chemistry*; D014443:Tyrosine / Q000737:chemistry
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; D010980:Platelet Membrane Glycoproteins; D017452:Receptors, IgG; C098341:platelet membrane glycoprotein VI; D014443:Tyrosine; D002772:Cholera Toxin