Evidence for cross-talk between glycoprotein VI and Gi-coupled receptors during collagen-induced platelet aggregation

Collagen-induced platelet aggregation is a complex process and involves syn ergistic action of integrins, immunoglobulin (19)-like receptors, G-protein coupled receptors and their ligands, most importantly collagen itself, thro mboxane A(2) (TXA(2)), and adenosine diphosphate (ADP), The precise role of each of these receptor systems in the overall processes of activation and aggregation, however, Is still poorly defined. Among the collagen receptors expressed on platelets, glycoprotein (GP) VI has been identified to play a crucial role in collagen-induced activation. GPVI is associated with the F cR gamma chain, which serves as the signal transducing unit of the receptor complex. It is well known that clustering of GPVI by highly specific agoni sts results in platelet activation and irreversible aggregation, but it is unclear whether collagen has the same effect on the receptor. This study sh ows that platelets from G alphaq-deficient mice, despite their severely imp aired response to collagen, normally aggregate on clustering of GPVI, sugge sting this not to be the principal mechanism by which collagen activates pl atelets. On the other hand, dimerization of GPVI by a monoclonal antibody ( JAQ1), which by itself did not induce aggregation, provided a sufficient st imulus to potentiate platelet responses to Gi-coupled, but not Gq-coupled, agonists, The combination of JAQ1 and adrenaline or ADP, but not serotonin, resulted in alpha (llb)beta (3)-dependent aggregation that occurred withou t intracellular calcium mobilization and shape change in the absence of G a lphaq or the P2Y(1) receptor. Together, these results provide evidence for a cross-talk between (dimerized) GPVI and Gi-coupled receptors during colla gen-induced platelet aggregation.