Cofilin

Cofilin is an actin-binding protein of the ADF/cofilin family that controls actin filament turnover in eukaryotic cells. In mammals it is represented primarily by cofilin-1 and cofilin-2, with actin depolymerizing factor (ADF, also called destrin) as a related family member. Cofilin binds to both G-actin and F-actin, with a preference for ADP-bound actin filaments, and can sever filaments and accelerate depolymerization. Through filament turnover, cofilin generates new barbed ends that promote localized actin polymerization, supporting processes such as cell migration and endocytosis.

Regulation of cofilin activity is largely controlled by phosphorylation at serine 3. Phosphorylation by LIM kinases (LIMK1/2) inactivates cofilin and reduces binding to actin, while dephosphorylation by SSH phosphatases or chronophin reactivates it. In its inactive form, phosphorylated cofilin can be sequestered by 14-3-3 proteins. Upstream signals from Rho family GTPases—including Rho, Rac, and Cdc42—coordinate LIMK activity via kinases such as ROCK and PAK, linking external cues to actin remodeling.

Cofilin is essential for normal development in many organisms and plays key roles in neuronal morphology and plasticity, immune cell motility, and epithelial cell migration. Dysregulation of cofilin activity is associated with pathological states, including cancer cell invasion and certain neurological conditions, reflecting its central role in active remodeling of the cytoskeleton.