近日，山东大学教授孙金鹏及其研究组揭示平衡感知需要一种力敏感的粘附GPCR。2025年2月18日，国际知名学术期刊《细胞研究》发表了这一成果。

该课题组研究人员发现G蛋白偶联受体（GPCR） LPHN2/ADGRL2在毛细胞顶膜上表达，对维持正常平衡至关重要。小鼠毛细胞中LPHN2的特异性缺失损害了平衡行为和MET反应。对毛细胞特异性LPHN2敲除小鼠和LPHN2特异性抑制剂的功能分析表明，LPHN2调节毛细胞顶端表面的尖端连接无关的MET电流。在异源体系统中的机制研究表明，LPHN2将力刺激转化为跨膜通道样蛋白1 （TMC1）的开放概率增加。LPHN2介导的力感触发谷氨酸释放和钙信号传导。重要的是，将LPHN2重新引入LPHN2缺陷小鼠的毛细胞可恢复前庭功能和MET反应。他们的数据显示，一种机械敏感的GPCR是平衡所必需的。

据了解，平衡感觉（平衡感）对哺乳动物感知和导航三维世界至关重要。前庭毛细胞的快速机电转导（MET）反应对于检测位置和运动至关重要。

附：英文原文

Title: A force-sensitive adhesion GPCR is required for equilibrioception

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

Issue&Volume: 2025-02-18

Abstract: Equilibrioception (sensing of balance) is essential for mammals to perceive and navigate the three-dimensional world. A rapid mechanoelectrical transduction (MET) response in vestibular hair cells is crucial for detecting position and motion. Here, we identify the G protein-coupled receptor (GPCR) 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 (TMC1). 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.

DOI: 10.1038/s41422-025-01075-x

Source: https://www.nature.com/articles/s41422-025-01075-x