Abstract：
Transient Receptor Potential (TRP) channels constitute a large superfamily of polymodal channel proteins with diverse roles in many physiological and sensory systems that function both as ionotropic and metabotropic receptors. From the early days of TRP channel discovery, membrane lipids were suggested to play a fundamental role in channel activation and regulation. A prominent example is the Drosophila TRP and TRP-like (TRPL) channels, which are predominantly expressed in the visual system of Drosophila. Light activation of the TRP and TRPL channels, the founding members of the TRP channel superfamily, requires activation of phospholipase Cβ (PLC), which hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) into Diacylglycerol (DAG) and Inositol 1, 4,5-trisphosphate (IP3). However, the events required for channel gating downstream of PLC activation are still under debate and led to several hypotheses regarding the mechanisms by which lipids gate the channels. Despite many efforts, compelling evidence of the involvement of DAG accumulation, PIP2 depletion or IP3-mediated Ca2+ release in light activation of the TRP/TRPL channels are still lacking. Exogeneous application of poly unsaturated fatty acids (PUFAs), a product of DAG hydrolysis was demonstrated as an efficient way to activate the Drosophila TRP/TRPL channels. However, compelling evidence for the involvement of PUFAs in physiological light-activation of the TRP/TRPL channels is still lacking. Light-induced mechanical force generation was measured in photoreceptor cells prior to channel opening. This mechanical force depends on PLC activity, suggesting that the enzymatic activity of PLC converting PIP2 into DAG generates membrane tension, leading to mechanical gating of the channels. In this review, we will present the roles of membrane lipids in light activation of Drosophila TRP channels and present the many advantages of this model system in the exploration of TRP channel activation under physiological conditions.
摘要：
瞬时受体电位（TRP）通道构成了一个大型的多峰通道蛋白超家族，在许多生理和感觉系统中具有不同的作用，这些系统既可以用作离子型受体，也可以用作代谢型受体。从TRP频道发现的早期开始，膜脂被认为在通道激活和调节中起着重要作用。一个突出的例子是果蝇TRP和TRP样（TRPL）通道，主要在果蝇的视觉系统中表达。TRP和TRPL通道的光活化，TRP频道超家族的创始成员，需要激活磷脂酶Cβ（PLC），将磷脂酰肌醇4,5-二磷酸酯（PIP2）水解为二酰基甘油（DAG）和肌醇1,4,5-三磷酸酯（IP3）。然而,PLC激活下游通道门控所需的事件仍在争论中，并导致了关于脂质门控通道的机制的几个假设。尽管做出了许多努力,有说服力的证据证明DAG的积累，在TRP/TRPL通道的光活化中，PIP2耗尽或IP3介导的Ca2释放仍然缺乏。多不饱和脂肪酸（PUFA）的外源应用，DAG水解产物被证明是激活果蝇TRP/TRPL通道的有效方法。然而,尚缺乏PUFA参与TRP/TRPL通道的生理光激活的令人信服的证据。在通道打开之前在感光细胞中测量光诱导的机械力产生。这种机械力取决于PLC的活动，表明PLC将PIP2转化为DAG的酶活性产生膜张力，导致通道的机械门控。在这次审查中,我们将介绍膜脂在果蝇TRP通道光激活中的作用，并介绍该模型系统在探索生理条件下TRP通道激活方面的许多优势。
