The Small GTPase Rap1b: A Bidirectional Regulator of Platelet Adhesion Receptors
Figure 1
Schematic diagram of the main pathways regulating Rap1b activation during platelet adhesion. The figure summarizes the major players involved in Rap1b activation mediated by platelet adhesion receptors. Downstream of integrin α 2β 1, PLCγ2 plays a critical role for Rap1b activation, which, however, requires also the Pyk2-mediated stimulation of PI3Kβ. Rap1 stimulates inside-out activation on integrin α IIbβ 3 and thus it is a central player in the crosstalk between these two integrin receptors. The collagen receptor GPVI stimulates Rap1b both directly, through PI3Kα and β, and indirectly through the autocrine stimulation of the P2Y12 receptor by secreted ADP. Moreover, activated Rap1b facilitates platelet granule secretion and ADP release. Rap1b-mediated inside-out activation of integrin α IIbβ 3 involves the Rap1 effector RIAM and the cytoskeletal proteins talin and kindlin. In turn, integrin α IIbβ 3 binding to fibrinogen stimulates an outside-in signaling able to promote Rap1b activation, which is an essential step for platelet spreading on fibrinogen.
