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:
果蝇光活化的瞬时受体电位(TRP)通道是通道蛋白的一个大家族的基础成员。果蝇TRP(dTRP)通道,在发现第一个哺乳动物TRP通道之前的二十年中,已经对其产生对光的电响应进行了详细的研究。因此,dTRP在TRP通道超家族的成员中是独特的,因为其生理作用和其激活基础的酶级联被确立。在本文中,我们概述了导致阐明dTRP作为光激活通道的研究,并专注于dTRP通道的主要生理特性,这是通过酶促反应的级联间接激活。这些详细的开创性研究,基于基因解剖方法,揭示果蝇TRP通道的光活化是由G蛋白偶联受体(GPCR)依赖性酶促级联介导的,其中磷脂酶Cβ(PLC)是关键成分。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,它直接被辣椒素激活,低pH和高温(>42°C)。这种激活机制显然与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级联的靶标。随后的研究表明,在生理条件下,TRPV1也是GPCR激活的PLC级联反应的目标。果蝇光活化TRP通道仍然是一个有用的实验范例,因为它作为光活化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,和参与这些通道激活的信号分子是可用的。