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作者

Zhao Yang Shu-Hua Zhou Qi-Yue Zhang Zhi-Chen Song Wen-Wen Liu Yu Sun Ming-Wei Wang Xiao-Long Fu Kong-Kai Zhu Ying Guan Jie-Yu Qi Xiao-Hui Wang Yu-Nan Sun Yan Lu Yu-Qi Ping Yue-Tong Xi Zhen-Xiao Teng Lei Xu Peng Xiao Zhi-Gang Xu Wei Xiong Wei Qin Wei Yang Fan Yi Ren-Jie Chai Xiao Yu null Jin-Peng Sun

作者单位

⁴Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China ⁶Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China ⁷Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China ⁹State Key Laboratory of Vascular Homeostasis and Remodeling, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China ¹³Department of Biophysics, and Department of Neurology of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China ¹⁴Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China ¹²School of Physics, State Key Laboratory of Crystal Materials, Shandong University, Jinan, Shandong, China ¹⁰Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Shandong University School of Life Sciences, Qingdao, Shandong, China ³Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China ¹¹Chinese Institute for Brain Research, Beijing, China ²State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, Advanced Institute for Life and Health Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, Jiangsu, China ⁸Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China ¹NHC Key Laboratory of Otorhinolaryngology, Qilu Hospital of Shandong University, and New Cornerstone Science Laboratory, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China ⁵Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

刊名

Cell Research

年份

2025

卷号

Vol.35 No.4

页码

243-264

ISSN

1001-0602

摘要

Equilibrioception is essential for mammals to perceive and navigate the three-dimensional world. A rapid mechanoelectrical transduction response in vestibular hair cells is crucial for detecting position and motion. Here, we identify the G protein-coupled receptor LPHN2/ADGRL2, expressed on the apical membrane of utricular hair cells, as essential for maintaining normal balance. Loss of LPHN2 specifically in hair cells impaired both balance behavior and the MET response in mice. Functional an...更多

Equilibrioception is essential for mammals to perceive and navigate the three-dimensional world. A rapid mechanoelectrical transduction response in vestibular hair cells is crucial for detecting position and motion. Here, we identify the G protein-coupled receptor LPHN2/ADGRL2, expressed on the apical membrane of utricular hair cells, as essential for maintaining normal balance. Loss of LPHN2 specifically in hair cells impaired both balance behavior and the MET response in mice. Functional analyses using hair-cell-specific Lphn2-knockout mice and an LPHN2-specific inhibitor suggest that LPHN2 regulates tip-link-independent MET currents at the apical surface of utricular hair cells. Mechanistic studies in a heterologous system show that LPHN2 converts force stimuli into increased open probability of transmembrane channel-like protein 1 . LPHN2-mediated force sensation triggers glutamate release and calcium signaling in utricular hair cells. Importantly, reintroducing LPHN2 into the hair cells of Lphn2-deficient mice restores vestibular function and MET response. Our data reveal that a mechanosensitive GPCR is required for equilibrioception.收起

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