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

• DOI: 10.1016/j.neuron.2017.12.041
• Publication Date: 2018-01-27T01:49:00Z
• Authors: Xiaomin Yue; Jian Zhao; Xiao Li; Yuedan Fan; Duo Duan; Xiaoyan Zhang; Wenjuan Zou; Yi Sheng; Ting Zhang; Qian Yang; Jianhong Luo; Shumin Duan; Rui Xiao; Lijun Kang
• Keywords: Neurons; 0301 basic medicine; Sexual Behavior, Animal; 03 medical and health sciences; Muscles; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Ion Channels; Membrane Potentials

Membrane excitability is a fundamentally important feature for all excitable cells including both neurons and muscle cells. However, the background depolarizing conductances in excitable cells, especially in muscle cells, are not well characterized. Although mutations in transmembrane channel-like (TMC) proteins TMC1 and TMC2 cause deafness and vestibular defects in mammals, their precise action modes are elusive. Here, we discover that both TMC-1 and TMC-2 are required for normal egg laying in C. elegans. Mutations in these TMC proteins cause membrane hyperpolarization and disrupt the rhythmic calcium activities in both neurons and muscles involved in egg laying. Mechanistically, TMC proteins enhance membrane depolarization through background leak currents and ectopic expression of both C. elegans and mammalian TMC proteins results in membrane depolarization. Therefore, we have identified an unexpected role of TMC proteins in modulating membrane excitability. Our results may provide mechanistic insights into the functions of TMC proteins in hearing loss and other diseases.