Regulated RIAM-Talin Engagement Controls Adhesion Stability and Mechanical Output

受调控的RIAM-Talin接合控制粘附稳定性和机械输出

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Abstract

RIAM (Rap1-GTP-interacting adaptor molecule) links Rap1 to talin-1 to promote integrin activation and is normally enriched at nascent adhesions. How the duration of RIAM-talin engagement influences adhesion dynamics and force transmission remains unclear. Here, we used a RIAM chimera in which the native talin-binding site was replaced with the talin-binding motif of Kank2 to enforce sustained talin association and redistribute RIAM modules to mature adhesions. This talin-tethered RIAM chimera enhanced integrin activation, accelerated both adhesion assembly and disassembly, reduced adhesion lifetime, increased the fraction of nascent adhesions nucleated by RIAM, and elevated cellular traction forces. Notably, while integrin activation by the chimera was largely Rap1-independent, Rap1 binding remained necessary for optimal adhesion turnover kinetics and full traction force generation. These findings demonstrate that prolonged talin engagement of RIAM is sufficient to reprogram adhesion dynamics and reveal a separable role for Rap1 in coordinating force transmission downstream of integrin activation. Together, our results highlight the importance of regulating the residence and engagement mode of RIAM at talin for controlling adhesion plasticity and mechanotransduction.

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