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tmc-1 编码一种钠离子敏感通道,该通道对于线虫的盐化学感觉是必需的。

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

机构信息

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.

出版信息

Nature. 2013 Feb 7;494(7435):95-99. doi: 10.1038/nature11845. Epub 2013 Jan 30.


DOI:10.1038/nature11845
PMID:23364694
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4021456/
Abstract

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.

摘要

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。

相似文献

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

Nature. 2013-1-30

[2]
Characterization of TMC-1 in C. elegans sodium chemotaxis and sodium conditioned aversion.

BMC Genet. 2020-3-30

[3]
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Neuron. 2016-7-6

[4]
Mammalian TRPV4 (VR-OAC) directs behavioral responses to osmotic and mechanical stimuli in Caenorhabditis elegans.

Proc Natl Acad Sci U S A. 2003-11-25

[5]
Ankyrin Is An Intracellular Tether for TMC Mechanotransduction Channels.

Neuron. 2020-4-22

[6]
TMC Proteins Modulate Egg Laying and Membrane Excitability through a Background Leak Conductance in C. elegans.

Neuron. 2018-1-27

[7]
The structure of the TMC-2 complex suggests roles of lipid-mediated subunit contacts in mechanosensory transduction.

Proc Natl Acad Sci U S A. 2024-2-20

[8]
Sequence variations and accessory proteins adapt TMC functions to distinct sensory modalities.

Neuron. 2024-9-4

[9]
Distinct functions of TMC channels: a comparative overview.

Cell Mol Life Sci. 2019-10-4

[10]
The G-protein gamma subunit gpc-1 of the nematode C.elegans is involved in taste adaptation.

EMBO J. 2002-3-1

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本文引用的文献

[1]
Neuromodulatory state and sex specify alternative behaviors through antagonistic synaptic pathways in C. elegans.

Neuron. 2012-8-23

[2]
Mechanotransduction in mouse inner ear hair cells requires transmembrane channel-like genes.

J Clin Invest. 2011-11-21

[3]
DEG/ENaC but not TRP channels are the major mechanoelectrical transduction channels in a C. elegans nociceptor.

Neuron. 2011-9-8

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Food sensitizes C. elegans avoidance behaviours through acute dopamine signalling.

EMBO J. 2011-2-8

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Time-lapse imaging and cell-specific expression profiling reveal dynamic branching and molecular determinants of a multi-dendritic nociceptor in C. elegans.

Dev Biol. 2010-6-9

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Hypoxia activates a latent circuit for processing gustatory information in C. elegans.

Nat Neurosci. 2010-4-18

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Nature. 2010-1-27

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Biochim Biophys Acta. 2009-8

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Functional asymmetry in Caenorhabditis elegans taste neurons and its computational role in chemotaxis.

Nature. 2008-7-3

[10]
Novel gating and sensitizing mechanism of capsaicin receptor (TRPV1): tonic inhibitory regulation of extracellular sodium through the external protonation sites on TRPV1.

J Biol Chem. 2008-4-4

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