Pathways for talin-mediated activation of integrins. In the unstimulated platelet, integrin αIIbβ3 exists in a resting state (does not bind ligand with high affinity) and talin exists in the cytosol in an autoinhibited state in which interaction between its rod (R) domain and its head (H) domain occludes the integrin-binding site in the head domain. Three pathways are known to relieve the autoinhibition of talin, allowing its recruitment to the cell membrane via a push-pull charge-dependent mechanism8 and to the integrin β subunit. The paper by Stritt et al1 indicates that the RIAM is dispensable for talin-mediated activation of integrin and the responses mediated by activated and occupied integrin αIIbβ3.
