Rychkov G, Barritt G J
School of Molecular and Biomedical Science, University of Adelaide, 5005 Adelaide, South Australia, Australia.
Handb Exp Pharmacol. 2007(179):23-52. doi: 10.1007/978-3-540-34891-7_2.
The full-length transient receptor (TRPC)1 polypeptide is composed of about 790 amino acids, and several splice variants are known. The predicted structure and topology is of an integral membrane protein composed of six transmembrane domains, and a cytoplasmic C- and N-terminal domain. The N-terminal domain includes three ankyrin repeat motifs. Antibodies which recognise TRPC1 have been developed, but it has been difficult to obtain antibodies which have high affinity and specificity for TRPC1. This has made studies of the cellular functions of TRPC1 somewhat difficult. The TRPC1 protein is widely expressed in different types of animal cells, and within a given cell is found at the plasma membrane and at intracellular sites. TRPC1 interacts with calmodulin, caveolin-1, the InsP3 receptor, Homer, phospholipase C and several other proteins. Investigations of the biological roles and mechanisms of action of TRPC1 have employed ectopic (over-expression or heterologous expression) of the polypeptide in addition to studies of endogenous TRPC1. Both approaches have encountered difficulties. TRPC1 forms heterotetramers with other TRPC polypeptides resulting in cation channels which are non-selective. TRPC1 may be: a component of the pore of store-operated Ca2+ channels (SOCs); a subsidiary protein in the pathway of activation of SOCs; activated by interaction with InsP3R; and/or activated by stretch. Further experiments are required to resolve the exact roles and mechanisms of activation of TRPC1. Cation entry through the TRPC1 channel is feed-back inhibited by Ca2+ through interaction with calmodulin, and is inhibited by Gd3+, La3+, SKF96365 and 2-APB, and by antibodies targeted to the external mouth of the TRPC1 pore. Activation of TRPC1 leads to the entry to the cytoplasmic space of substantial amounts of Na+ as well as Ca2+. A requirement for TRPC1 is implicated in numerous downstream cellular pathways. The most clearly described roles are in the regulation of growth cone turning in neurons. It is concluded that TRPC1 is a most interesting protein because of the apparent wide variety of its roles and functions and the challenges posed to those attempting to elucidate its primary intracellular functions and mechanisms of action.
全长瞬时受体电位（TRPC）1多肽由约790个氨基酸组成，已知有几种剪接变体。预测的结构和拓扑结构是一种由六个跨膜结构域以及一个胞质C端和N端结构域组成的整合膜蛋白。N端结构域包含三个锚蛋白重复基序。已经开发出识别TRPC1的抗体，但很难获得对TRPC1具有高亲和力和特异性的抗体。这使得对TRPC1细胞功能的研究有些困难。TRPC1蛋白在不同类型的动物细胞中广泛表达，在给定细胞内，它存在于质膜和细胞内位点。TRPC1与钙调蛋白、小窝蛋白-1、肌醇三磷酸受体、Homer、磷脂酶C和其他几种蛋白质相互作用。除了对内源性TRPC1的研究外，对TRPC1生物学作用和作用机制的研究还采用了该多肽的异位表达（过表达或异源表达）。这两种方法都遇到了困难。TRPC1与其他TRPC多肽形成异源四聚体，产生非选择性阳离子通道。TRPC1可能是：储存操纵性Ca2+通道（SOCs）孔道的一个组成部分；SOCs激活途径中的辅助蛋白；通过与肌醇三磷酸受体相互作用而激活；和/或通过拉伸激活。需要进一步的实验来确定TRPC1的确切作用和激活机制。通过TRPC1通道的阳离子内流通过与钙调蛋白相互作用被Ca2+反馈抑制，并被钆离子、镧离子、SKF96365和2-氨基苯甲酸盐以及针对TRPC1孔道外口的抗体抑制。TRPC1的激活导致大量Na+以及Ca2+进入细胞质空间。TRPC1的需求与众多下游细胞途径有关。最明确描述的作用是在神经元生长锥转向的调节中。结论是，TRPC1是一种非常有趣的蛋白质，因为其作用和功能明显多种多样，并且给试图阐明其主要细胞内功能和作用机制的人带来了挑战。
