细胞大小和形态主要由细胞溶质和离子浓度变化控制，通过渗透压变化使细胞内液体处于平衡状态。美国耶鲁大学科学家领导的研究小组在最新一期Cell发表封面文章，应用一种新的蛋白质组定量技术确定了细胞控制钾离子和氯离子出入细胞的调节方法。
蛋白质磷酸化是一种常见的蛋白质可逆修饰。研究发现，在正常环境中，细胞膜上的通道蛋白完全磷酸化，钾离子和氯离子不能被转运；当改变细胞随处环境时，通道蛋白迅速去磷酸化，并表现出转运活性。
研究人员还表示，了解这种转运机制或许可以用于治疗镰刀贫血症。转运蛋白磷酸化机制同样存在于神经细胞对于神经递质和离子的选择透过调节。（生物谷Bioon.com）
生物谷推荐原始出处：
Cell, Volume 138, Issue 3, 525-536, 7 August 2009 doi:10.1016/j.cell.2009.05.031
Sites of Regulated Phosphorylation that Control K-Cl Cotransporter Activity
Jesse Rinehart1,5,Yelena D. Maksimova2,Jessica E. Tanis3,Kathryn L. Stone5,6,Caleb A. Hodson1,Junhui Zhang1,Mary Risinger7,Weijun Pan4,Dianqing Wu4,Christopher M. Colangelo5,6,Biff Forbush3,Clinton H. Joiner7,Erol E. Gulcicek5,6,Patrick G. Gallagher2andRichard P. Lifton1,5,,
1 Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA
2 Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06510, USA
3 Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06510, USA
4 Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA
5 Yale/National Heart, Lung, and Blood Institute Proteomics Center, Yale University, New Haven, CT 06511, USA
6 Keck Biotechnology Resource Laboratory, Yale University, New Haven, CT 06511, USA
7 Cincinnati Comprehensive Sickle Cell Center, Division of Hematology/Oncology, University of Cincinnati College of Medicine and Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA
Modulation of intracellular chloride concentration ([Cl]i) plays a fundamental role in cell volume regulation and neuronal response to GABA. Cl exit via K-Cl cotransporters (KCCs) is a major determinant of [Cl]I; however, mechanisms governing KCC activities are poorly understood. We identified two sites in KCC3 that are rapidly dephosphorylated in hypotonic conditions in cultured cells and human red blood cells in parallel with increased transport activity. Alanine substitutions at these sites result in constitutively active cotransport. These sites are highly phosphorylated in plasma membrane KCC3 in isotonic conditions, suggesting that dephosphorylation increases KCC3's intrinsic transport activity. Reduction of WNK1 expression via RNA interference reduces phosphorylation at these sites. Homologous sites are phosphorylated in all human KCCs. KCC2 is partially phosphorylated in neonatal mouse brain and dephosphorylated in parallel with KCC2 activation. These findings provide insight into regulation of [Cl]i and have implications for control of cell volume and neuronal function.
