Regulation of Voltage-gated Proton Channel

电压门控质子通道的调节

• 批准号: 10565941
• 负责人: Liang Hong
• 金额: $ 31.98万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-08 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10565941
• 关键词: Acids; Action Potentials; Adaptive Immune System; Affinity; Alveolar Cell; Binding; Binding Sites; Biochemical; Biophysical Process; Biophysics; Cell membrane; Cell physiology; Cells; Charge; Co-Immunoprecipitations; Compensation; Complex; Disease; Dissociation; Elements; Epithelial Cells; Family; Goals; Integral Membrane Protein; Interferons; Ion Channel Gating; Kinetics; Lung; Mediating; Membrane; Molecular; Mutagenesis; Mutation Analysis; NADPH Oxidase; Neurons; Permeability; Phagocytes; Pharmacology; Physiological; Physiology; Play; Production; Proteins; Protons; RNA Interference; Reactive Oxygen Species; Regulation; Research; Respiratory Burst; Role; Scanning; Shapes; Site; Snails; Sperm Capacitation; Testing; Tissues; Yeasts; airway surface liquid; biophysical properties; cell type; channel blockers; design; drug development; in vivo; insight; knock-down; member; mutant; neutrophil; novel; pH Homeostasis; pH gradient; paralogous gene; screening; sperm cell; therapy development; voltage; yeast two hybrid system

Abstract The voltage-gated Hv1 proton channel is a member of voltage-gated ion channel family, it plays a key role in the acid extrusion from excitable and non-excitable cells and regulate pH homeostasis in a variety of cell types. The Hv1 proton channel provides charge and pH compensation during the respiratory burst of the phagocyte NADPH oxidase and controls production of reactive oxygen species in phagocytes, it mediates proton efflux at the pulmonary alveolar cell membrane and acidifies excessively alkaline airway surface liquid in the airway cells. Hv1 is found to be a sperm flagellar regulator of intracellular pH, and play a crucial role in sperm capacitation. In addition, Hv1 activity is required for acid extrusion to shape action potentials in snail neurons. Studies have shown that biophysical properties and functions of the Hv1 channel are not identical in a variety of tissues, the distinct manifestations of native voltage-gated proton channels in different cell types indicate the existence of modulatory partners modulating the Hv1 proton channel's function. We recently identified a family of transmembrane protein as the Hv1 channel interactor. We discovered that the presence of the transmembrane protein alters the Hv1 channel's activity and modulates the channel's voltage-dependent gating. The goal of this proposal is designed to determine the effects of the transmembrane protein on the Hv1 channel physiology, biophysics, and pharmacology. The proposed research will establish the physiological relevance of Hv1 channel regulation by transmembrane modulators and shed light on novel voltage-gated ion channel regulatory mechanisms.

摘要 电压门控性Hv1质子通道是电压门控性离子通道家族的一员， 在酸从可兴奋和不可兴奋细胞中排出和调节pH中起关键作用 在多种细胞类型中的稳态。Hv1质子通道提供电荷和pH 在吞噬细胞NADPH氧化酶和对照的呼吸爆发期间的补偿 吞噬细胞中产生活性氧，介导肺部质子流出 肺泡细胞膜，并酸化气道细胞中的过度碱性气道表面液体。 Hv1是精子鞭毛细胞内pH的调节因子，在精子中起着重要的作用 获能此外，Hv1活性是酸挤出所必需的，以形成动作电位。 蜗牛神经元研究表明，Hv1通道的生物物理特性和功能 在各种组织中并不相同，天然电压门控质子的不同表现 不同细胞类型中的通道表明存在调节Hv1的调节伴侣 质子通道的功能。我们最近发现了一个跨膜蛋白家族，即Hv1 通道交互器。我们发现，跨膜蛋白的存在改变了Hv1 通道的活动和调节通道的电压依赖性门控。这个目标 本研究旨在确定跨膜蛋白对Hv1通道的影响 生理学、生物物理学和药理学。这项研究将建立生理学 跨膜调节剂对Hv1通道调节的相关性， 电压门控离子通道调节机制。