Abstract
Filopodia assemble unique integrin-adhesion complexes as they sense and attach to the surrounding extracellular matrix. Integrin activation is essential for filopodia stability; however, the regulation of integrin activity within filopodia is poorly defined. Using structured illumination and scanning electron microscopy, we observed that active integrin is spatially confined to filopodia tips and inactive integrin localises throughout the filopodia shaft. RNAi depletion of integrin regulators identified FERM domain containing talin and MYO10 as critical regulators of filopodia function. Importantly, deletion of MYO10-FERM ablates the active pool of integrin from filopodia, indicating that MYO10-FERM domain is required for integrin activation but not for integrin transport to filopodia tips. Yet, remarkably, the MYO10-FERM domain binds both α and β integrin tails restricting integrin activation. Swapping MYO10-FERM with talin-FERM leads to an over-activation of integrin receptors in filopodia. Our observations demonstrate a complex regulation of integrin activity, at filopodia tips, via MYO10-FERM domain and challenge the concept of MYO10-dependent integrin transport in filopodia.
Competing Interest Statement
The authors have declared no competing interest.