Rap1-GTP-interacting adaptor molecule (RIAM) is dispensable for platelet integrin activation and function in mice

Abstract

Platelet aggregation at sites of vascular injury is essential for hemostasis but also thrombosis. Platelet adhesiveness is critically dependent on agonist-induced inside-out activation of heterodimeric integrin receptors by amechanisminvolving the recruitment of talin-1 to the cytoplasmic integrin tail. Experiments in heterologous cells have suggested a critical role of Rap1-guanosine triphosphate-interacting adaptor molecule (RIAM) for talin-1 recruitment and thus integrin activation, but direct in vivo evidence to support this has been missing. We generated RIAM-null mice and found that they are viable, fertile, and apparently healthy. Unexpectedly, platelets from these mice show unaltered b3- and b1-integrin activation and consequently normal adhesion and aggregation responses under static andflowconditions.Similarly,hemostasis andarterial thrombus formationwere indistinguishable between wild-type and RIAM-nullmice. These results reveal that RIAMis dispensable for integrin activation and function in mouse platelets, strongly suggesting the existence of alternative mechanisms of talin-1 recruitment.