Lee Jeong Han, Perez-Flores Maria C, Park Seojin, Kim Hyo Jeong, Chen Yingying, Kang Mincheol, Kersigo Jennifer, Choi Jinsil, Thai Phung N, Woltz Ryan, Perez-Flores Dolores Columba, Perkins Guy, Sihn Choong-Ryoul, Trinh Pauline, Zhang Xiao-Dong, Sirish Padmini, Dong Yao, Feng Wayne Wei, Pessah Isaac N, Dixon Rose E, Sokolowski Bernd, Fritzsch Bernd, Chiamvimonvat Nipavan, Yamoah Ebenezer N
Department of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno, NV 89557.
Prestige Biopharma, 11-12F, 44, Myongjigukje7-ro, Gangseo-gu, Busan, South Korea 67264.
Res Sq. 2023 Jul 12:rs.3.rs-2287052. doi: 10.21203/rs.3.rs-2287052/v1.
The inner ear is the hub where hair cells transduce sound, gravity, and head acceleration stimuli carried by neural codes to the brain. Of all the senses, hearing and balance, which rely on mechanosensation, are the fastest sensory signals transmitted to the central nervous system. The mechanoelectrical transducer (MET) channel in hair cells is the entryway for the sound-balance-brain interface, but the channel's composition has eluded biologists due to its complexity. Here, we report that the mouse utilizes Piezo1 (Pz1) and Piezo2 (Pz2) isoforms as central components of the MET complex. The Pz channel subunits are expressed in hair-cell stereocilia, are co-localized and co-assembled, and are essential components of the MET complex and including integration with the transmembrane channel (Tmc1/2) protein. Mice expressing non-functional and but not functional at the ROSA26 locus under the control of hair-cell promoters, have impaired auditory and vestibular traits that can only be explained if Pz channel multimers are integral to the MET complex. We affirm that Pz protein subunits constitute MET channels and that functional interactions with components of the MET complex yield current properties resembling hair-cell MET currents. Our results demonstrate Pz is a MET channel component central to interacting with MET complex proteins. Results account for the MET channel pore and complex.
内耳是毛细胞将由神经编码携带的声音、重力和头部加速度刺激转化为神经信号传递至大脑的枢纽。在所有感官中，依赖机械感觉的听觉和平衡感是传递至中枢神经系统最快的感觉信号。毛细胞中的机械电换能器（MET）通道是声音 - 平衡 - 大脑界面的入口，但由于其复杂性，该通道的组成一直未被生物学家所明确。在此，我们报告小鼠利用Piezo1（Pz1）和Piezo2（Pz2）亚型作为MET复合物的核心成分。Pz通道亚基在毛细胞静纤毛中表达，共定位且共同组装，并且是MET复合物的重要组成部分，包括与跨膜通道（Tmc1/2）蛋白整合。在毛细胞启动子控制下，在ROSA26位点表达无功能而非有功能的Pz通道的小鼠，具有受损的听觉和前庭特征，只有当Pz通道多聚体是MET复合物的组成部分时才能解释这些特征。我们证实Pz蛋白亚基构成MET通道，并且与MET复合物成分的功能相互作用产生类似于毛细胞MET电流的电流特性。我们的结果表明Pz是与MET复合物蛋白相互作用的核心MET通道成分。研究结果解释了MET通道孔和复合物的情况。
