細(xì)胞大小和形態(tài)主要由細(xì)胞溶質(zhì)和離子濃度變化控制，通過(guò)滲透壓變化使細(xì)胞內(nèi)液體處于平衡狀態(tài),。美國(guó)耶魯大學(xué)科學(xué)家領(lǐng)導(dǎo)的研究小組在最新一期Cell發(fā)表封面文章，應(yīng)用一種新的蛋白質(zhì)組定量技術(shù)確定了細(xì)胞控制鉀離子和氯離子出入細(xì)胞的調(diào)節(jié)方法,。
蛋白質(zhì)磷酸化是一種常見(jiàn)的蛋白質(zhì)可逆修飾,。研究發(fā)現(xiàn)，在正常環(huán)境中,，細(xì)胞膜上的通道蛋白完全磷酸化,，鉀離子和氯離子不能被轉(zhuǎn)運(yùn)；當(dāng)改變細(xì)胞隨處環(huán)境時(shí),，通道蛋白迅速去磷酸化,，并表現(xiàn)出轉(zhuǎn)運(yùn)活性。
研究人員還表示，了解這種轉(zhuǎn)運(yùn)機(jī)制或許可以用于治療鐮刀貧血癥,。轉(zhuǎn)運(yùn)蛋白磷酸化機(jī)制同樣存在于神經(jīng)細(xì)胞對(duì)于神經(jīng)遞質(zhì)和離子的選擇透過(guò)調(diào)節(jié),。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
