Chronophin, a novel HAD-type serine protein phosphatase, regulates cofilin-dependent actin dynamics
Chronophin, a novel HAD-type serine protein phosphatase, regulates cofilin-dependent actin dynamics
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DOI：
10.1038/ncb1201
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发表时间：
2005-01-01
影响因子：
21.3
通讯作者：
Bokoch, GM
中科院分区：
文献类型：
--
作者：
Gohla, A;Birkenfeld, J;Bokoch, GM
Cofilin是肌动蛋白细胞骨架动力学的关键调节因子，其活性由单个丝氨酸残基的磷酸化控制。我们报道了盐酸脱卤酶（HAD）超家族中一种独特的cofilin激活磷酸酶——chronophin （CIN）的生化分离。CIN直接高特异性地使cofilin去磷酸化，并在运动细胞和分裂细胞中与cofilin共定位。CIN活性的丧失阻断了cofilin的磷酸化循环，稳定了F-actin结构并导致大量细胞分裂缺陷。我们的研究结果确定了哺乳动物hd型磷酸酶的生理磷酸化丝氨酸蛋白底物，并证明CIN是cofilin介导的肌动蛋白重组的重要新调节剂。
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.