Yildirim E, Birnbaumer L
Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA.
Handb Exp Pharmacol. 2007(179):53-75. doi: 10.1007/978-3-540-34891-7_3.
TRPC (canonical transient receptor potential) channels are the closest mammalian homologs of Drosophila TRP and TRP-like channels. TRPCs are rather nonselective Ca2+ permeable cation channels and affect cell functions through their ability to mediate Ca2+ entry into cells and their action to collapse the plasma membrane potentials. In neurons the latter function leads to action potentials. The mammalian genome codes for seven TRPCs of which TRPC2 is the largest with the most restricted pattern of expression and has several alternatively spliced variants. Expressed in model cells, TRPC2 mediates both receptor- and store depletion-triggered Ca2+ entry. TRPC2 is unique among TRPCs in that its complete gene has been lost from the Old World monkey and human genomes, in which its remnants constitute a pseudogene. Physiological roles for TRPC2 have been studied in mature sperm and the vomeronasal sensory system. In sperm, TRPC2 is activated by the sperm's interaction with the oocyte's zona pellucida, leading to entry of Ca2+ and activation of the acrosome reaction. In the vomeronasal sensory organ (VNO), TRPC2 was found to constitute the transduction channel activated through signaling cascade initiated by the interaction of pheromones with V1R and V2R G protein-coupled receptors on the dendrites of the sensory neurons. V1Rs and V2Rs, the latter working in conjunction with class I MHC molecules, activate G(i)- and G(o)-type G proteins which in turn trigger activation of TRPC2, initiating an axon potential that travels to the axonal terminals. The signal is then projected to the glomeruli of the auxiliary olfactory bulb from where it is carried first to the amygdala and then to higher cortical cognition centers. Immunocytochemistry and gene deletion studies have shown that (1) the V2R-G(o)-MHCIb-beta2m pathway mediates male aggressive behavior in response to pheromones; (2) the V1R-G(i2) pathway mediates mating partner recognition, and (3) these differences have an anatomical correlate in that these functional components are located in anatomically distinct compartments of the VNO. Interestingly, these anatomically segregated signaling pathways use a common transduction channel, TRPC2.
TRPC（典型瞬时受体电位）通道是果蝇TRP和TRP样通道在哺乳动物中最相似的同源物。TRPC是相当非选择性的Ca2+通透阳离子通道，通过介导Ca2+进入细胞的能力及其使质膜电位崩溃的作用来影响细胞功能。在神经元中，后一种功能导致动作电位。哺乳动物基因组编码七种TRPC，其中TRPC2最大，表达模式最受限，并且有几个可变剪接变体。在模型细胞中表达时，TRPC2介导受体和储存耗竭触发的Ca2+内流。TRPC2在TRPC中是独特的，因为其完整基因在旧世界猴和人类基因组中已经丢失，在这些基因组中其残余部分构成一个假基因。TRPC2的生理作用已在成熟精子和犁鼻器感觉系统中进行了研究。在精子中，TRPC2通过精子与卵母细胞透明带的相互作用而被激活，导致Ca2+进入并激活顶体反应。在犁鼻器感觉器官（VNO）中，发现TRPC2构成通过信息素与感觉神经元树突上的V1R和V2R G蛋白偶联受体相互作用引发的信号级联激活的转导通道。V1R和V2R，后者与I类MHC分子协同作用，激活G(i)型和G(o)型G蛋白，进而触发TRPC2的激活，启动向轴突末端传播的轴突电位。然后信号投射到辅助嗅球的肾小球，从那里首先传递到杏仁核，然后传递到更高的皮质认知中心。免疫细胞化学和基因敲除研究表明：（1）V2R-G(o)-MHCIb-β2m途径介导对信息素的雄性攻击行为；（2）V1R-G(i2)途径介导交配伙伴识别；（3）这些差异在解剖学上有相关性，因为这些功能成分位于VNO的解剖学上不同的隔室中。有趣的是，这些解剖学上分离的信号通路使用一个共同的转导通道TRPC2。
