Cell Biology Division, MRC Laboratory of Molecular Biology, Hills Road, Cambridge UK.
Department of Biomedical Sciences, Korea University College of Medicine, Seoul 136-705, Korea.
Nature. 2013 Feb 7;494(7435):95-99. doi: 10.1038/nature11845. Epub 2013 Jan 30.
Transmembrane channel-like (TMC) genes encode a broadly conserved family of multipass integral membrane proteins in animals. Human TMC1 and TMC2 genes are linked to human deafness and required for hair-cell mechanotransduction; however, the molecular functions of these and other TMC proteins have not been determined. Here we show that the Caenorhabditis 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, C. elegans 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 probable ionotropic sensory receptor.
跨膜通道样(TMC)基因编码一类广泛保守的多跨整合膜蛋白家族,存在于动物中。人类 TMC1 和 TMC2 基因与人类耳聋有关,是毛细胞机械转导所必需的;然而,这些和其他 TMC 蛋白的分子功能尚未确定。在这里,我们表明,秀丽隐杆线虫的 tmc-1 基因编码一种钠离子传感器,它专门在盐味化学感觉中发挥作用。tmc-1 在 ASH 多模态回避神经元中表达,它是盐诱发神经元活动和行为性回避高浓度 NaCl 所必需的。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排斥物)没有反应,表明它在盐感觉中具有特定的作用。当在哺乳动物细胞培养中表达时,秀丽隐杆线虫的 TMC-1 产生一种主要由高细胞外钠离子激活的阳离子电流,但不能被其他阳离子或不带电荷的小分子激活。因此,TMC-1 既是体内盐感觉所必需的,也是体外产生钠离子敏感通道所必需的,这表明它可能是一种离子型感觉受体。
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