Control of the actin cytoskeleton is critical for many cellular processes, particularly cell motility. The actin-depolymerizing factor cofilin is inhibited by phosphorylation. To better understand its regulation, Gohla et al. used classical protein-purification techniques to isolate a protein with phosphatase activity toward cofilin phosphorylated on serine 3. The enzyme they isolated is a member of the haloacid dehalogenase (HAD) superfamily of phosphotransferases. These phosphatases have an unusual catalytic mechanism and were not previously implicated in serine dephosphorylation in mammals. The phosphatase, which the authors name chronophin (CIN), appears to be a physiologically relevant regulator of cofilin. Overexpression of CIN decreased amounts of phosphocofilin in HeLa cells. Depletion of CIN by RNA interference increased the amount of phosphocofilin, increased the amount of Factin, stabilized membrane protrusions and stress fibers, and caused abnormalities in cell division. The findings place new emphasis on understanding the HAD proteins and suggest that CIN could be a therapeutic target in diseases where control of the actin cytoskeleton is disrupted.
A. Gohla, J. Birkenfeld, G. M. Bokoch, Chronophin, a novel HAD-type serine protein phosphatase, regulates cofilin-dependent actin dynamics. Nat. Cell Biol. 7, 21-29 (2005). [PubMed]