The light-activated TRP channel: the founding member of the TRP channel superfamily.

IF 1.8 4区 医学 Q3 GENETICS & HEREDITY
Baruch Minke, William L Pak
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引用次数: 3

Abstract

The Drosophila light-activated Transient Receptor Potential (TRP) channel is the founding member of a large and diverse family of channel proteins. The Drosophila TRP (dTRP) channel, which generates the electrical response to light has been investigated in a great detail two decades before the first mammalian TRP channel was discovered. Thus, dTRP is unique among members of the TRP channel superfamily because its physiological role and the enzymatic cascade underlying its activation are established. In this article we outline the research leading to elucidation of dTRP as the light activated channel and focus on a major physiological property of the dTRP channel, which is indirect activation via a cascade of enzymatic reactions. These detailed pioneering studies, based on the genetic dissection approach, revealed that light activation of the Drosophila TRP channel is mediated by G-Protein-Coupled Receptor (GPCR)-dependent enzymatic cascade, in which phospholipase C β (PLC) is a crucial component. This physiological mechanism of Drosophila TRP channel activation was later found in mammalian TRPC channels. However, the initial studies on the mammalian TRPV1 channel indicated that it is activated directly by capsaicin, low pH and hot temperature (>42 °C). This mechanism of activation was apparently at odds with the activation mechanism of the TRPC channels in general and the Drosophila light activated TRP/TRPL channels in particular, which are target of a GPCR-activated PLC cascade. Subsequent studies have indicated that under physiological conditions TRPV1 is also target of a GPCR-activated PLC cascade in the generation of inflammatory pain. The Drosophila light-activated TRP channel is still a useful experimental paradigm because its physiological function as the light-activated channel is known, powerful genetic techniques can be applied to its further analysis, and signaling molecules involved in the activation of these channels are available.

光激活TRP通道:TRP通道超家族的创始成员。
果蝇光激活瞬时受体电位(TRP)通道是一个庞大而多样的通道蛋白家族的创始成员。果蝇TRP (dTRP)通道产生对光的电反应,早在第一个哺乳动物TRP通道被发现的20年前,人们就对其进行了详细的研究。因此,在TRP通道超家族的成员中,dTRP是独一无二的,因为它的生理作用和激活它的酶级联是确定的。在本文中,我们概述了导致阐明dTRP作为光激活通道的研究,并重点介绍了dTRP通道的一个主要生理特性,即通过一系列酶促反应间接激活。这些详细的开创性研究,基于遗传解剖方法,揭示了果蝇TRP通道的光激活是由g蛋白偶联受体(GPCR)依赖性酶级联介导的,其中磷脂酶C β (PLC)是一个关键组成部分。果蝇TRP通道激活的这种生理机制后来在哺乳动物TRPC通道中被发现。然而,对哺乳动物TRPV1通道的初步研究表明,它直接被辣椒素、低pH和高温(>42°C)激活。这种激活机制显然与一般的TRPC通道的激活机制不一致,特别是果蝇光激活的TRP/TRPL通道,它们是gpcr激活的PLC级联的目标。随后的研究表明,在生理条件下,TRPV1也是gpcr激活的PLC级联反应产生炎性疼痛的靶标。果蝇光激活TRP通道仍然是一个有用的实验范例,因为它作为光激活通道的生理功能是已知的,强大的遗传技术可以应用于其进一步分析,并且参与这些通道激活的信号分子是可用的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of neurogenetics
Journal of neurogenetics 医学-神经科学
CiteScore
4.40
自引率
0.00%
发文量
13
审稿时长
>12 weeks
期刊介绍: The Journal is appropriate for papers on behavioral, biochemical, or cellular aspects of neural function, plasticity, aging or disease. In addition to analyses in the traditional genetic-model organisms, C. elegans, Drosophila, mouse and the zebrafish, the Journal encourages submission of neurogenetic investigations performed in organisms not easily amenable to experimental genetics. Such investigations might, for instance, describe behavioral differences deriving from genetic variation within a species, or report human disease studies that provide exceptional insights into biological mechanisms
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