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Cell Mol Life Sci. 2019 Nov;76(21):4221-4232. doi: 10.1007/s00018-019-03214-1. Epub 2019 Oct 4.

Distinct functions of TMC channels: a comparative overview.

Author information

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.
2
Department of Aging and Geriatric Research, Institute on Aging, University of Florida, Gainesville, FL, USA.
3
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. kanglijun@zju.edu.cn.
4
Department of Aging and Geriatric Research, Institute on Aging, University of Florida, Gainesville, FL, USA. rxiao@ufl.edu.
5
Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, FL, USA. rxiao@ufl.edu.
6
Center for Smell and Taste, University of Florida, Gainesville, FL, USA. rxiao@ufl.edu.

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.

KEYWORDS:

C. elegans; Drosophila; Hearing; Mechanosensation; Membrane excitability; TMC channels; Zebrafish

PMID:
31584127
DOI:
10.1007/s00018-019-03214-1
[Indexed for MEDLINE]

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