Involvement of GD3 in platelet activation. A novel association with Fcgamma receptor.
Gangliosides are sialic acid-containing glycosphingolipids present in the outer leaflet of the plasma membrane of many cell types where they modulate adhesive processes. The main population of glycolipids in resting platelets is represented by ganglioside M3 (GM3). It has been demonstrated that following platelet activation ganglioside D3 (GD3) is rapidly formed from the GM3 pool. The present study was designed to evaluate the link between platelet activation and GD3 expression and to verify whether this ganglioside might play a role in modulating signal transduction events. Our results suggest that following platelet activation, GD3 is rapidly expressed on the platelet surface and internalised to the cytoskeleton where it transiently associates first with the Src family tyrosine kinase Lyn then with the Fc receptor gamma chain. This sequence of events ultimately leads to an enhanced CD32 (the Fc receptor isoform present in platelets) expression on the platelet membrane. These data drive us to speculate that GD3 might act as second messenger in the activatory cascade, which leads to CD32 expression and triggers platelet adhesion and spreading to the subendothelial matrix.
Martini
F
F
Laboratory of Platelet Pathophysiology, Department of Experimental Medicine and Pathology, University of Rome La Sapienza, Viale Regina Elena 324, 00161 Rome, Italy.
Riondino
S
S
Pignatelli
P
P
Gazzaniga
P P
PP
Ferroni
P
P
Lenti
L
L
D000244:Adenosine Diphosphate / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology; D001095:Arachidonic Acids / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005732:Gangliosides / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism; D015539:Platelet Activation; D017452:Receptors, IgG / Q000187:drug effects / Q000378:metabolism*; D019061:src-Family Kinases / Q000187:drug effects / Q000378:metabolism
D001095:Arachidonic Acids; D004791:Enzyme Inhibitors; D005732:Gangliosides; D017452:Receptors, IgG; C081565:arachidonyltrifluoromethane; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; C026226:ganglioside, GD3; D003094:Collagen; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D010741:Phospholipases A