Regulation of Voltage-gated Proton Channel

电压门控质子通道的调节

基本信息

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
项目类别：
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

项目摘要

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.

抽象的电压门控HV1质子通道是电压门控离子通道家族的成员在可激发和非驱取的细胞中的酸挤出中起关键作用并调节pH 各种细胞类型的稳态。 HV1质子通道提供电荷和pH 吞噬细胞NADPH氧化酶的呼吸爆发期间的补偿和对照在吞噬细胞中产生活性氧，它介导了肺部的质子外排肺泡细胞膜并酸化气道细胞中的碱性气道表面液体。发现HV1是细胞内pH的精子鞭毛调节剂，并且在精子中起着至关重要的作用电容。此外，酸挤出需要HV1活性才能塑造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多种组织中并不相同，这是天然电压门控质子的明显表现不同细胞类型中的通道表明调制伙伴的存在调节HV1 质子通道的功能。我们最近确定了跨膜蛋白家族为HV1 通道交互器。我们发现跨膜蛋白的存在改变了HV1 通道的活动并调节通道的电压依赖性门。目标的目标建议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。拟议的研究将建立生理通过跨膜调节器调节HV1通道调节的相关性，并阐明了新型电压门控离子通道调节机制。