Li Bingxue, Li Songling, Zheng Honglan, Yan Zhiqiang
State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institute of Brain Science, School of Life Sciences, Fudan University, Shanghai 200438, China.
Institute of Molecular Physiology, Shenzhen Bay Laboratory, Shenzhen 518132, China.
Proc Natl Acad Sci U S A. 2021 Dec 7;118(49). doi: 10.1073/pnas.2106459118.
Auditory transduction is mediated by chordotonal (Cho) neurons in larvae, but the molecular identity of the mechanotransduction (MET) channel is elusive. Here, we established a whole-cell recording system of Cho neurons and showed that two transient receptor potential vanilloid (TRPV) channels, Nanchung (NAN) and Inactive (IAV), are essential for MET currents in Cho neurons. NAN and IAV form active ion channels when expressed simultaneously in S2 cells. Point mutations in the pore region of NAN-IAV change the reversal potential of the MET currents. Particularly, residues 857 through 990 in the IAV carboxyl terminus regulate the kinetics of MET currents in Cho neurons. In addition, TRPN channel NompC contributes to the adaptation of auditory transduction currents independent of its ion-conduction function. These results indicate that NAN-IAV, rather than NompC, functions as essential pore-forming subunits of the native auditory transduction channel in and provide insights into the gating mechanism of MET currents in Cho neurons.
听觉转导由幼虫中的弦音（Cho）神经元介导，但机械转导（MET）通道的分子身份尚不清楚。在这里，我们建立了Cho神经元的全细胞记录系统，并表明两个瞬时受体电位香草酸（TRPV）通道，南春（NAN）和失活（IAV），对Cho神经元中的MET电流至关重要。NAN和IAV在S2细胞中同时表达时形成活性离子通道。NAN-IAV孔区域的点突变改变了MET电流的反转电位。特别是，IAV羧基末端的857至990位残基调节Cho神经元中MET电流的动力学。此外，TRPN通道NompC有助于听觉转导电流的适应性，而与其离子传导功能无关。这些结果表明，NAN-IAV而非NompC是果蝇中天然听觉转导通道的必需孔形成亚基，并为Cho神经元中MET电流的门控机制提供了见解。
