Regulation of the formin INF2 by actin monomers and calcium-calmodulin.

ABSTRACT: In response to increased intracellular calcium, the formin INF2 polymerizes 20-30% of the total cellular actin pool within 30 sec, suggesting robust regulation. INF2 regulation requires an auto-inhibitory interaction between the N-terminal Diaphanous Inhibitory Domain (DID) and the C-terminal Diaphanous Auto-regulatory Domain (DAD). DID mutations are dominantly linked to two human diseases, and constitutively activate INF2. However, DAD binding to actin monomers competes with DID binding, disrupting regulation. Here, we use a novel cell-free assay for detailed investigation of INF2 regulation. Contrary to our previous findings, INF2 inhibition does not require CAP proteins but does require actin 'buffering' by monomer-binding proteins such as profilin or thymosin. INF2 is activated by calc

SUBMITTER: Lee M 

PROVIDER: S-EPMC12632326 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature