The CLIC-1 Chloride Channel: Structure and Function

CLIC-1 氯离子通道：结构和功能

• 批准号: 6858651
• 负责人: JOHN C EDWARDS
• 金额: $ 15.45万
• 依托单位: SAINT LOUIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2005-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6858651
• 关键词: beta adrenergic receptor; chloride channels; conformation; gel filtration chromatography; high performance liquid chromatography; hydropathy; lipid bilayer membrane; mass spectrometry; membrane activity; membrane lipids; membrane permeability; membrane proteins; membrane structure; phospholipids; protein isoforms; protein localization; protein structure function; solubility; vesicle /vacuole

DESCRIPTION (provided by applicant): Chloride channel proteins are essential to a host of cellular functions and chloride channel dysfunction is known to be involved in the pathogenesis of a number of human disease states. We have identified and begun to characterize a family of chloride channel proteins which are structurally unrelated to other known chloride channels. One member of this family, CLIC-1, is expressed in many cell types and is very highly expressed in the apical domain of renal proximal tubule cells. Subcellular localization studies indicate that it is present in membrane compartments along the endosomal pathway. We have recently demonstrated that recombinant CLIC-1 functions as a chloride selective channel when purified from bacteria and reconstituted in phospholipid membranes. Unlike typical ion channel proteins, CLIC proteins are present in cells both in a membrane inserted form and in a soluble form in the cytoplasm. Over the past several years, a number of membrane proteins have been reported to be able to assume conformations which are soluble in aqueous solution. In some instances, it is clear that these proteins can partition between membrane-inserted and soluble states and that this partitioning is important in regulation of the activity of these proteins. We have now found that CLIC-1 is capable of inserting into phospholipid membranes from the aqueous phase and this inserted CLIC-1 can function as a chloride channel. In this grant application, we propose to study the biochemical basis and biological relevance of functional membrane insertion of this important protein.

描述（由申请人提供）：氯通道蛋白对许多细胞功能至关重要，氯通道功能障碍已知与许多人类疾病状态的发病机制有关。我们已经确定并开始表征一个与其他已知氯离子通道在结构上无关的氯离子通道蛋白家族。该家族的一个成员CLIC-1在许多细胞类型中表达，并在肾近端小管细胞的顶域高度表达。亚细胞定位研究表明，它存在于沿内体途径的膜室中。我们最近已经证明，当从细菌中纯化并在磷脂膜中重组时，重组CLIC-1作为氯离子选择通道发挥作用。