Gohla Antje, Birkenfeld Jörg, Bokoch Gary M
The Scripps Research Institute, Departments of Immunology and Cell Biology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Nat Cell Biol. 2005 Jan;7(1):21-9. doi: 10.1038/ncb1201. Epub 2004 Dec 5.
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.
丝切蛋白是肌动蛋白细胞骨架动力学的关键调节因子，其活性受单个丝氨酸残基磷酸化的控制。我们报告了生物钟素（CIN）的生化分离，它是卤代酸脱卤酶（HAD）超家族中一种独特的丝切蛋白激活磷酸酶。CIN以高特异性直接使丝切蛋白去磷酸化，并在运动和分裂细胞中与丝切蛋白共定位。CIN活性的丧失会阻断丝切蛋白的磷酸循环，稳定F-肌动蛋白结构并导致大量细胞分裂缺陷。我们的研究结果确定了一种哺乳动物HAD型磷酸酶的生理性磷酸化丝氨酸蛋白底物，并证明CIN是丝切蛋白介导的肌动蛋白重组的重要新型调节因子。
