Gudermann Thomas, Mederos y Schnitzler Michael, Dietrich Alexander
Institut für Pharmakologie und Toxikologie, Fachbereich Medizin, Philipps-Universität Marburg, Karl-von-Frisch-Str. 1, D-35033 Marburg, Germany.
Sci STKE. 2004 Jul 20;2004(243):pe35. doi: 10.1126/stke.2432004pe35.
Many hormones and neurotransmitters elicit an increase in the intracellular calcium concentration by binding to phospholipase C-linked G protein-coupled receptors. Activated receptors signal to calcium-permeable cation channels in the plasma membrane, which are distinct from those engaged by emptying of intracellular stores of calcium. The TRPC family of the mammalian homologs of the Drosophila transient receptor potential (TRP) cation channel represents likely molecular correlates underlying receptor-operated cation entry. While all TRPC family members are gated in a phospholipase C-dependent manner, the exact activation mechanism still remains elusive, although lipids such as diacylglycerol and polyunsaturated fatty acids are potential diffusible messengers. Functional TRPC channel complexes in the plasma membrane are thought to be composed of four distinct subunits whose stoichiometry and composition under physiological conditions are still largely unknown. However, recent progress in defining the combinatorial rules of TRPC channel assembly may lead to the identification of TRPC-dependent ion fluxes in living cells. Because of the large number of TRP proteins and their frequently overlapping functional characteristics, the central question is whether TRP proteins are functionally interchangeable or whether unique physiological roles can be ascribed to them. Receptor-operated cation entry is critically involved in the control of airway and vascular smooth muscle tone; hence, TRPC proteins are promising new drug targets.
许多激素和神经递质通过与磷脂酶C偶联的G蛋白偶联受体结合，引起细胞内钙浓度升高。活化的受体向质膜中的钙通透阳离子通道发出信号，这些通道与细胞内钙库排空所涉及的通道不同。果蝇瞬时受体电位（TRP）阳离子通道的哺乳动物同源物TRPC家族可能是受体操纵的阳离子进入的潜在分子关联物。虽然所有TRPC家族成员都以磷脂酶C依赖的方式门控，但确切的激活机制仍然难以捉摸，尽管二酰基甘油和多不饱和脂肪酸等脂质是潜在的可扩散信使。质膜中的功能性TRPC通道复合物被认为由四个不同的亚基组成，其在生理条件下的化学计量和组成仍然很大程度上未知。然而，在确定TRPC通道组装的组合规则方面的最新进展可能会导致在活细胞中识别TRPC依赖性离子通量。由于TRP蛋白数量众多且功能特征经常重叠，核心问题是TRP蛋白在功能上是否可互换，或者是否可以赋予它们独特的生理作用。受体操纵的阳离子进入关键参与气道和血管平滑肌张力的控制；因此，TRPC蛋白是有前景的新药物靶点。
