The Rap1-RIAM pathway prefers β2 integrins.

In vitro studies strongly implicate the talin-binding Ras-related protein 1 (Rap1) effector, Rap1-guanosine triphosphate–interacting adapter molecule (RIAM), in integrin activation. Yet, the RIAM knockout mouse is viable and fertile and exhibits no platelet adhesion or aggregation defects, casting doubt on the in vivo role of RIAM. In this issue of Blood, Su et al and Klapproth et al now show that RIAM is required for β2 integrin–dependent leukocyte adhesion and trafficking in vitro and in vivo, but apparently not for all Rap- and talin-meditated activation of β1 and β3 integrins.