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.

摘要

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_在第一个哺乳动物 TRP 通道被发现之前的二十年，已经对产生对光的电响应的 TRP (dTRP) 通道进行了非常详细的研究。因此，dTRP 在 TRP 通道超家族的成员中是独一无二的，因为它的生理作用和激活它的酶促级联已经建立。在这篇文章中，我们概述了导致阐明 dTRP 作为光激活通道的研究，并重点关注 dTRP 通道的主要生理特性，即通过一系列酶促反应间接激活。这些基于基因解剖方法的详细开创性研究揭示了果蝇的光激活TRP 通道由 G 蛋白偶联受体 (GPCR) 依赖性酶促级联介导，其中磷脂酶 C β (PLC) 是关键组分。这种果蝇TRP 通道激活的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 值和高温 (>42 °C) 激活。这种激活机制显然与一般 TRPC 通道和果蝇的激活机制不一致特别是光激活的 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 级联在炎症疼痛产生中的目标。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。