Rhodocytin (aggretin) activates platelets lacking alpha(2)beta(1) integrin, glycoprotein VI, and the ligand-binding domain of glycoprotein Ib alpha

Although alpha (2)beta (1) integrin (glycoprotein Ia/IIa) has been establis hed as a platelet collagen receptor, its role in collagen-induced platelet activation has been controversial. Recently, it has been demonstrated that rhodocytin (also termed aggretin), a snake venom toxin purified from the ve nom of Calloselasma rhodostoma, induces platelet activation that can be blo cked by monoclonal antibodies against alpha (2)beta (1) integrin, This find ing suggested that clustering of alpha (2)beta (1) integrin by rhodocytin i s sufficient to induce platelet activation and led to the hypothesis that c ollagen may activate platelets by a similar mechanism. In contrast to these findings, we provided evidence that rhodocytin does not bind to alpha (2)b eta (1) integrin, Here we show that the Cre/loxP-mediated loss of p, integr in on mouse platelets has no effect on rhodocytin-induced platelet activati on, excluding an essential role of ru,p, integrin in this process. Furtherm ore, proteolytic cleavage of the 45-kDa N-terminal domain of glycoprotein ( GP) Ib alpha either on normal or on Pi-null platelets had no significant ef fect on rhodocytin-induced platelet activation. Moreover, mouse platelets l acking both alpha (2)beta (1) integrin and the activating collagen receptor GPVI responded normally to rhodocytin, Finally, even after additional prot eolytic removal of the 45-kDa N-terminal domain of GPIb alpha rhodocytin in duced aggregation of these platelets. These results demonstrate that rhodoc ytin induces platelet activation by mechanisms that are fundamentally diffe rent from those induced by collagen.