Regulation of Cofilin Activity by CaMKII and Calcineurin

Cofilin promotes actin filament turnover by severing and depolymerizing actin filaments. Cofilin is inactivated by phosphorylation on Ser-3 by LIM-kinase1 (LIMK1) and is activated when protein phosphatase Slingshot-1L (SSH1L) dephosphorylates this residue. The authors have shown that Ca2+-induced cofilin dephosphorylation is mediated by calcineurin (Cn)-dependent activation of SSH1L. In this study, Ca2+/calmodulin-dependent protein kinase II (CaMKII) is shown to negatively regulate SSH1L activity and bind to SSH1L in a complex with 14-3-3. Phosphorylation of LIMK1 by CaMKII and its subsequent activation regulates the subcellular localization of SSH1L. Based on these findings, the authors suggest that CaMKII and Cn provide a switch-like mechanism that controls Ca2+-dependent LIMK1, SSH1L and cofilin activation, and subsequently actin cytoskeletal reorganization.