FCHo2, instead of talin, enables inside-out activation of integrin ɑvβ5 in curved adhesions.

ABSTRACT: Inside-out activation of integrins is crucial for transducing mechanical forces through the extracellular ligand-integrin-talin-F-actin axis. Extensive studies have shown that talin is the essential player in this process by binding to the intracellular tail of β integrins. Here, we show that, while talin binding is essential for inside-out integrin activation in focal adhesions, it is dispensable in curved adhesions - a distinct adhesion architecture that is exclusively mediated by integrin αvβ5 and selectively formed at curved membranes. Instead, a curvature-sensing protein FCHo2 binds to the HDRRE motif in the cytoplasmic tail of integrin β5 (ITGβ5) and inside-out activates integrin αvβ5 in curved adhesions. Intriguingly, FCHo2 does not bind to a similar motif in the homologous integrin

SUBMITTER: Lu CH 

PROVIDER: S-EPMC12694587 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature