title: Lipid rafts orchestrate signaling by the platelet receptor glycoprotein VI.
abstract: The platelet collagen receptor glycoprotein VI (GPVI) couples to the immune receptor adaptor Fc receptor gamma-chain (FcRgamma) and signals using many of the same intracellular signaling molecules as immune receptors. Studies of immune receptor signaling have revealed a critical role for specialized areas of the cell membrane known as lipid rafts, which are enriched in essential signaling molecules. However, the role of lipid rafts in signaling in nonimmune cells such as platelets remains poorly defined. This study shows that GPVI-FcRgamma does not constitutively associate with rafts, but is recruited to lipid rafts following receptor stimulation in both GPVI-expressing RBL-2H3 cells and human platelets. FcRgamma is required for GPVI association with lipid rafts, as mutant GPVI receptors that do not couple to FcRgamma were unable to associate with lipid rafts after receptor clustering. Following GPVI stimulation in platelets, virtually all phosphorylated FcRgamma was found in lipid rafts, but inhibition of FcRgamma phosphorylation did not block receptor association with lipid rafts. This work demonstrates that lipid rafts orchestrate GPVI receptor signaling in platelets in a manner analogous to immune cell receptors and supports a model of GPVI signaling in which FcRgamma phosphorylation is controlled by ligand-dependent association with lipid rafts.
authors.affiliation: Division of Cardiology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6100, USA.
authors.forename: Darren
authors.initials: D
authors.lastname: Locke
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Changdong
authors.initials: C
authors.lastname: Liu
authors.forename: Mark L
authors.initials: ML
authors.lastname: Kahn
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D006801:Humans; D008055:Lipids / Q000502:physiology*; D051379:Mice; D010766:Phosphorylation; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D008055:Lipids; D010980:Platelet Membrane Glycoproteins; D017452:Receptors, IgG; C098341:platelet membrane glycoprotein VI