Chronophin, a novel HAD-type serine protein phosphatase, regulates cofilin-dependent actin dynamics.
Cofilin is a key regulator of actin cytoskeletal dynamics whose activity is controlled by phosphorylation of a single serine residue. We report the biochemical isolation of chronophin (CIN), a unique cofilin-activating phosphatase of the haloacid dehalogenase (HAD) superfamily. CIN directly dephosphorylates cofilin with high specificity and colocalizes with cofilin in motile and dividing cells. Loss of CIN activity blocks phosphocycling of cofilin, stabilizes F-actin structures and causes massive cell division defects. Our findings identify a physiological phospho-serine protein substrate for a mammalian HAD-type phosphatase and demonstrate that CIN is an important novel regulator of cofilin-mediated actin reorganization.
Gohla
Antje
A
The Scripps Research Institute, Departments of Immunology and Cell Biology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Birkenfeld
Jörg
J
Bokoch
Gary M
GM
D008841:Actin Cytoskeleton / Q000378:metabolism*; D051339:Actin Depolymerizing Factors; D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D015536:Down-Regulation / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D006867:Hydrolases / Q000737:chemistry / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D010766:Phosphorylation; D011554:Pseudopodia / Q000378:metabolism; D034622:RNA Interference; D011817:Rabbits; D012694:Serine / Q000378:metabolism
D051339:Actin Depolymerizing Factors; D000199:Actins; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D008840:Microfilament Proteins; D012694:Serine; D006867:Hydrolases; C496428:PDXP protein, human; D010749:Phosphoprotein Phosphatases; C034507:2-haloacid dehalogenase