Functional role of TRPC proteins in native systems: implications from knockout and knock-down studies
Functional role of TRPC proteins in native systems: implications from knockout and knock-down studies
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DOI：
10.1113/jphysiol.2005.092999
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发表时间：
2005-08-15
影响因子：
5.5
通讯作者：
Flockerzi, V
中科院分区：
文献类型：
--
作者：
Freichel, M;Vennekens, R;Flockerzi, V
有关瞬时受体电位通道(TRPC)蛋白功能的现有数据表明，这些蛋白是原代细胞中激动剂激活的和磷脂酶C依赖的阳离子进入途径的基本成分，这些途径有助于细胞内钙离子的升高。此外，各种TRPC蛋白已经被分配了大量的生物学功能，包括机械感觉活动(TRPC1)、趋化轴突引导(TRPC1和TRPC3)、信息素感知和性行为和社会行为的调节(TRPC2)、血管张力的内皮依赖性调节、内皮通透性和神经递质释放(TRPC4)、轴突生长(TRPC5)、调节血管和肺的平滑肌张力以及调节肾脏的足细胞结构和功能(TRPC6)。缺乏特异性阻断或激活TRPC蛋白的化合物影响了对原代细胞中TRPC功能的分析。因此，我们集中于(I)TRPC缺陷小鼠品系的研究，(Ii)通过使用反义寡核苷酸或RNA干扰的基因沉默方法获得的数据，(Iii)使用显性负TRPC结构的表达实验，以及(Iv)与人类疾病相关的TRPC基因突变的最新数据。
Available data on transient receptor potential channel (TRPC) protein functions indicate that these proteins represent essential constituents of agonist-activated and phospholipase C-dependent cation entry pathways in primary cells which contribute to the elevation of cytosolic Ca2+. In addition, a striking number of biological functions have already been assigned to the various TRPC proteins, including mechanosensing activity (TRPC1), chemotropic axon guidance (TRPC1 and TRPC3), pheromone sensing and the regulation of sexual and social behaviour (TRPC2), endothelial-dependent regulation of vascular tone, endothelial permeability and neurotransmitter release (TRPC4), axonal growth (TRPC5), modulation of smooth muscle tone in blood vessels and lung and regulation of podocyte structure and function in the kidney (TRPC6). The lack of compounds which specifically block or activate TRPC proteins impairs the analysis of TRPC function in primary cells. We therefore concentrate in this contribution on (i) studies of TRPC-deficient mouse lines, (ii) data obtained by gene-silencing approaches using antisense oligonucleotides or RNA interference, (iii) expression experiments employing dominant negative TRPC constructs, and (iv) recent data correlating mutations of TRPC genes associated with human disease.