tmc-1 encodes a sodium-sensitive channel required for salt chemosensation in C. elegans.

tmc-1 encodes a sodium-sensitive channel required for salt chemosensation in C. elegans.
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TMC-1编码在秀丽隐杆线虫中盐化学一致所需的钠敏感通道。

DOI:
10.1038/nature11845
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发表时间:
2013-02-07
期刊:
影响因子:
64.8
通讯作者:
Schafer, William R.
Schafer, William R.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Chatzigeorgiou, Marios;Bang, Sangsu;Hwang, Sun Wook;Schafer, William R.

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TMC基因在动物中编码广泛保守的多通道整合膜蛋白家族。人类TMC 1和TMC 2是毛细胞机械转导所需的耳聋基因;然而,这些和其他TMC蛋白的分子功能尚未确定。我们在这里表明,C。线虫TMC-1基因编码一种钠感受器,其在盐味化学感受中特异性地起作用。TMC-1在ASH多模态回避神经元中表达,其中它是盐诱发的神经元活动和高浓度NaCl的行为回避所需的。然而,TMC-1对ASH神经元感知的其他刺激(包括高渗透压和化学驱避剂)的反应没有影响,表明在盐感觉中具有特定作用。当在哺乳动物细胞培养物中表达时,TMC-1产生主要由高细胞外钠激活的阳离子电导,但不被其他阳离子或不带电的小分子激活。因此,TMC-1是体内盐感觉所必需的,并且足以在体外产生钠敏感通道,将其鉴定为可能的候选离子型感觉受体。
TMC genes encode a broadly-conserved family of multipass integral membrane proteins in animals. Human TMC1 and TMC2 are deafness genes required for hair cell mechantransduction; however, the molecular functions of these and other TMC proteins have not been determined. We show here that the C. elegans TMC-1 gene encodes a sodium sensor that functions specifically in salt taste chemosensation. TMC-1 is expressed in the ASH polymodal avoidance neurons, where it is required for salt-evoked neuronal activity and behavioural avoidance of high concentrations of NaCl. However, tmc-1 has no effect on responses to other stimuli sensed by the ASH neurons including high osmolarity and chemical repellents, indicating a specific role in salt sensation. When expressed in mammalian cell culture, TMC-1 generates a predominantly cationic conductance activated by high extracellular sodium but not by other cations or uncharged small molecules. Thus, TMC-1 is both necessary for salt sensation in vivo and sufficient to generate a sodium-sensitive channel in vitro, identifying it as a likely candidate ionotropic sensory receptor.
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