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Distinct functions of TMC channels: a comparative overview

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Abstract

In the past two decades, transmembrane channel-like (TMC) proteins have attracted a significant amount of research interest, because mutations of Tmc1 lead to hereditary deafness. As evolutionarily conserved membrane proteins, TMC proteins are widely involved in diverse sensorimotor functions of many species, such as hearing, chemosensation, egg laying, and food texture detection. Interestingly, recent structural and physiological studies suggest that TMC channels may share a similar membrane topology with the Ca2+-activated Cl− channel TMEM16 and the mechanically activated OSCA1.2/TMEM63 channel. Namely, these channels form dimers and each subunit consists of ten transmembrane segments. Despite this important structural insight, a key question remains: what is the gating mechanism of TMC channels? The major technical hurdle to answer this question is that the reconstitution of TMC proteins as functional ion channels has been challenging in mammalian heterologous systems. Since TMC channels are conserved across taxa, genetic studies of TMC channels in model organisms such as C. elegans, Drosophila, and zebrafish may provide us critical information on the physiological function and regulation of TMCs. Here, we present a comparative overview on the diverse functions of TMC channels in different species.

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Funding

The work in the Xiao lab is supported by the American Cancer Society Research Scholar Grant (RSG-17-171-01-DMC), UF Center for Smell and Taste Pilot Grant, and the American Federation for Aging Research (AFAR) Research Grant (17146). The work in the Kang lab is supported by the National Foundation of Natural Science of China (31771113, 31900736, 31800878), the Fundamental Research Funds for the Central Universities (2018FZA7004), China Postdoctoral Science Foundation (2018M640551, 2018M642412, 2019T120503, 2019T120505), the 111 project, and the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2018PT31041).

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Authors and Affiliations

  1. Department of Neurosurgery of the First Affiliated Hospital, Institute of Neuroscience, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, China

    Xiaomin Yue & Lijun Kang

  2. Department of Aging and Geriatric Research, Institute on Aging, University of Florida, Gainesville, FL, USA

    Yi Sheng & Rui Xiao

  3. Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, FL, USA

    Rui Xiao

  4. Center for Smell and Taste, University of Florida, Gainesville, FL, USA

    Rui Xiao

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  1. Xiaomin Yue
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Yue, X., Sheng, Y., Kang, L. et al. Distinct functions of TMC channels: a comparative overview. Cell. Mol. Life Sci. 76, 4221–4232 (2019). https://doi.org/10.1007/s00018-019-03214-1

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