Myosin-X and Talin Modulate Integrin Activity at Filopodia Tips

Filopodia assemble unique integrin-adhesion complexes to sense the extracellular matrix. However, mechanisms of integrin localization and regulation in filopodia are poorly defined. Here, we observed that active integrins accumulate at tip myosin-X(MYO10)-positive while inactive uniformly distributed. RNAi depletion 10 activity modulators identified talin as principal activator filopodia. Deletion MYO10-FERM domain, or mutation β1-integrin-binding residues within, revealed MYO10 facilitating activation but not transport alone could activate integrins, potentially due dual binding both ɑ- β-integrin tails. As swapping with talin-FERM enabled filopodia, our data indicate an integrin-binding FERM domain coupled a myosin motor is core requirement for Therefore, propose two-step model filopodia: receptor tethering by followed talin-mediated activation.