作者
Bifeng Pan, Nurunisa Akyuz, Xiao-Ping Liu, Yukako Asai, Carl Nist-Lund, Kiyoto Kurima, Bruce H Derfler, Bence György, Walrati Limapichat, Sanket Walujkar, Lahiru N Wimalasena, Marcos Sotomayor, David P Corey, Jeffrey R Holt
发表日期
2018/8/22
期刊
Neuron
卷号
99
期号
4
页码范围
736-753. e6
出版商
Elsevier
简介
The proteins that form the permeation pathway of mechanosensory transduction channels in inner-ear hair cells have not been definitively identified. Genetic, anatomical, and physiological evidence support a role for transmembrane channel-like protein (TMC) 1 in hair cell sensory transduction, yet the molecular function of TMC proteins remains unclear. Here, we provide biochemical evidence suggesting TMC1 assembles as a dimer, along with structural and sequence analyses suggesting similarity to dimeric TMEM16 channels. To identify the pore region of TMC1, we used cysteine mutagenesis and expressed mutant TMC1 in hair cells of Tmc1/2-null mice. Cysteine-modification reagents rapidly and irreversibly altered permeation properties of mechanosensory transduction. We propose that TMC1 is structurally similar to TMEM16 channels and includes ten transmembrane domains with four domains, S4–S7 …
学术搜索中的文章
B Pan, N Akyuz, XP Liu, Y Asai, C Nist-Lund, K Kurima… - Neuron, 2018