Constitutive and functional association of the platelet collagen receptor glycoprotein VI-Fc receptor gamma-chain complex with membrane rafts.
The platelet collagen receptor glycoprotein (GP) VI-Fc receptor gamma-chain (FcRgamma) complex transduces signals in an immunoreceptorlike manner. We examined a role for the Triton X-100-insoluble membrane rafts in GPVI-FcRgamma complex signaling. Methyl-beta-cyclodextrin (MbetaCD)-induced disruption of the membrane rafts inhibited not only platelet aggregation and secretion but also tyrosine phosphorylation of signaling molecules on stimulation through the GPVI-FcRgamma complex. The GPVI-FcRgamma complex was constitutively associated with membrane rafts wherein the Src family kinases and LAT were also present. Their association was not affected by the complex engagement but was highly sensitive to MbetaCD treatment. Thus, we provide the first evidence that the GPVI-FcRgamma complex is constitutively and functionally associated with membrane rafts.
Ezumi
Yasuharu
Y
Department of Hematology and Oncology, Clinical Sciences for Pathological Organs, Graduate School of Medicine, Kyoto University, Japan.
Kodama
Kumi
K
Uchiyama
Takashi
T
Takayama
Hiroshi
H
D001792:Blood Platelets / Q000378:metabolism / Q000648:ultrastructure; D002499:Centrifugation, Density Gradient; D003094:Collagen / Q000494:pharmacology; D003435:Crotalid Venoms / Q000494:pharmacology; D003505:Cyclodextrins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D037181:Lectins, C-Type; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D015539:Platelet Activation / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D017452:Receptors, IgG / Q000378:metabolism* / Q000502:physiology; D047392:beta-Cyclodextrins
D003435:Crotalid Venoms; D003505:Cyclodextrins; D037181:Lectins, C-Type; D010980:Platelet Membrane Glycoproteins; D017452:Receptors, IgG; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; C098341:platelet membrane glycoprotein VI; C028890:convulxin; D003094:Collagen