The intimate and controversial relationship between voltage-gated proton channels and the phagocyte NADPH oxidase.
The intimate and controversial relationship between voltage-gated proton channels and the phagocyte NADPH oxidase.
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DOI：
10.1111/imr.12437
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发表时间：
2016-09
影响因子：
8.7
通讯作者：
DeCoursey TE
中科院分区：
文献类型：
--
作者：
DeCoursey TE
在我的科学生涯中，最令人着迷和兴奋的时期之一是剖析两种膜转运蛋白（NADPH氧化酶复合物和电压门控质子通道（HV 1））之间的共生关系。当我进入这个领域的时候，对NADPH氧化酶的理解已经取得了实质性的进展，但是全世界只有极少数的专家知道HV 1。1991年，我在哺乳动物细胞中发现了第一个质子流，如果这项工作要得到资助，我需要找到这些分子的明确功能。亨德森、查普尔及其同事在1987-1988年的发现为他们假设吞噬细胞呼吸爆发期间两种分子的相互作用提供了极好的机会。简而言之，这两种转运蛋白的功能都是通过跨膜移动电荷来实现的：NADPH氧化酶移动电子，HV 1移动质子。电生NADPH氧化酶活性对膜电位和pH的影响强烈地自我限制了这种酶。幸运的是，这两种结果都能特异性地激活HV 1，而HV 1的活性抵消了这两种结果，这是一种阴阳关系。尽管从1995年开始的十年中，许多人认为相反，但这是两个独立的分子，尽管它们在吞噬细胞中功能上相互依赖，但它们独立发挥作用。NADPH氧化酶和HV 1之间的关系已经成为一个范例，有点令人惊讶的是，现在已经远远超出了吞噬细胞NADPH氧化酶-活性氧（ROS）的工业强度生产者-到无数其他细胞，产生数量级更少的ROS用于信号传导目的。这些细胞及其七种NADPH氧化酶（NOX）亚型提供了一个广阔的机械模糊领域，将占据未来几年的研究。
One of the most fascinating and exciting periods in my scientific career entailed dissecting the symbiotic relationship between two membrane transporters, the NADPH oxidase complex and voltage gated proton channels (HV1). By the time I entered this field, there had already been substantial progress toward understanding NADPH oxidase, but HV1 were known only to a tiny handful of cognoscenti around the world. Having identified the first proton currents in mammalian cells in 1991, I needed to find a clear function for these molecules if the work was to become fundable. The then-recent discoveries of Henderson, Chappell, and colleagues in 1987–1988 that led them to hypothesize interactions of both molecules during the respiratory burst of phagocytes provided an excellent opportunity. In a nutshell, both transporters function by moving electrical charge across the membrane: NADPH oxidase moves electrons and HV1 moves protons. The consequences of electrogenic NADPH oxidase activity on both membrane potential and pH strongly self-limit this enzyme. Fortunately, both consequences specifically activate HV1, and HV1 activity counteracts both consequences, a kind of yin-yang relationship. Notwithstanding a decade starting in 1995 when many believed the opposite, these are two separate molecules that function independently despite their being functionally interdependent in phagocytes. The relationship between NADPH oxidase and HV1 has become a paradigm that somewhat surprisingly has now extended well beyond the phagocyte NADPH oxidase -- an industrial strength producer of reactive oxygen species (ROS) -- to myriad other cells that produce orders of magnitude less ROS for signaling purposes. These cells with their seven NADPH oxidase (NOX) isoforms provide a vast realm of mechanistic obscurity that will occupy future studies for years to come.
DOI：
10.1085/jgp.20028706
发表时间：
2002-12
期刊：
The Journal of general physiology
影响因子：
--
作者：
Touret N;Grinstein S
通讯作者：
Grinstein S
影响因子：
3.8
作者：
DeCoursey, Thomas E;Morgan, Deri;Cherny, Vladimir V
通讯作者：
Cherny, Vladimir V