Sodium Channel Biogenesis

钠通道生物发生

• 批准号: 7623696
• 负责人: Rebecca P Hughey
• 金额: $ 22.62万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7623696
• 关键词: Address; Affect; Aldosterone; Alveolar; Alveolus; Amiloride; Anabolism; Binding; Biogenesis; Blood Pressure; Cell membrane; Cell surface; Cleaved cell; Cytoplasm; Cytosol; Distal; Duct (organ) structure; Endopeptidases; Endoplasmic Reticulum; Endoplasmic Reticulum Degradation Pathway; Extracellular Domain; Extracellular Fluid; Hypertension; Hypotension; Ion Channel; Kidney; Lesion; Liquid substance; Mediating; Membrane; Nephrons; Numbers; Peptide Hydrolases; Peptides; Polysaccharides; Polyubiquitination; Probability; Process; Property; Proteins; Proteolytic Processing; Quality Control; Regulation; Research; Role; Site; Sodium Channel; Surface; System; Toxin; Urine; Yeasts; abstracting; alveolar epithelium; epithelial Na+ channel; extracellular; gain of function mutation; loss of function mutation; multicatalytic endopeptidase complex; prevent; research study; stoichiometry

Abstract Epithelial Na+ channel (ENaCs) are expressed in the aldosterone-sensitive distal nephron where they serve as the final site of renal Na+ reabsorption and have a key role in the regulation of extracellular fluid volume and blood pressure. ENaCs are also expressed throughout the airway and in alveoli, where they mediate Na+ reabsorption and have a critical role in regulating the volume of airway and alveolar fluids. Channel assembly appears to be an inefficient process, and quality control mechanisms within the ER have an important role in preventing exit of misfolded channel subunits from the ER while promoting the exit of properly assembled oligomeric channels for delivery to the cell surface. Channel subunits undergo post-translational processing that includes cleavage by proteases. Proposed studies in Aim 1 will define quality control mechanisms within the ER that targets ENaC subunits for degradation. Proposed studies in Aim 2 will define the processing of ENaC subunits and regulation of channel activity by proteases. These studies should generate new information regarding the regulation of ENaC biogenesis and post-translational processing that provide additional levels of control of the cellular and surface pool of Na+ channels and of channel gating.

摘要 上皮Na+通道（ENaCs）在醛固酮敏感的远端肾单位中表达， 它们作为肾脏Na+重吸收的最终位点，在调节 细胞外液量和血压。ENaC也在整个气道中表达 在肺泡中，它们介导Na+重吸收，并在调节 气道和肺泡液的体积。通道组装似乎是一个效率低下的过程， 和质量控制机制内的ER有一个重要的作用，防止退出 错误折叠的通道亚单位从ER，同时促进出口的正确组装 用于递送至细胞表面的寡聚体通道。通道亚基在翻译后 包括蛋白酶切割的加工。目标1中拟议的研究将定义质量 ER内靶向ENaC亚基降解的控制机制。提出 目标2中的研究将定义ENaC亚基的加工和通道活性的调节 蛋白酶这些研究应该产生关于ENaC调节的新信息 生物发生和翻译后加工，提供了额外的控制水平， Na+通道和通道门控的细胞和表面池。