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Updated: Jan 12, 2026

Morphological and Functional Evaluation of Ribbon Synapses at Specific Frequency Regions of the Mouse Cochlea
Published on: May 10, 2019
The force-sensing GPCR LPHN2 is indispensable for normal auditory function
Shu-Hua Zhou1, Ming-Wei Wang2, Zhi-Chen Song3
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 250012, China; Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China; State Key Laboratory of Vascular Homeostasis and Remodeling, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
Abstract:
The conversion of force sensation into electrical signals via mechano-electrical transduction (MET) is considered the key step in auditory perception. Here, we find that the G-protein-coupled receptor (GPCR) LPHN2/ADGRL2 is expressed at the tips of stereocilia in cochlear hair cells and is associated with MET channel components. Hair-cell-specific LPHN2 deficiency causes hearing loss and impaired MET responses. A specific inhibitor of LPHN2 also reversibly blocks the MET response. Mechanistically, the administration of force to LPHN2 activates TMC1 through physical interaction and causes conformational changes in TMC1. Furthermore, the sensing of force by LPHN2 stimulates the Ca2+ response and neurotransmitter release in hair cells. Finally, expression of LPHN2-GAIN in cochlear hair cells of Lphn2-deficient mice prevents hearing loss. Our work provides evidence that the GPCR can play modulatory roles in the auditory process through a TMC1-coupled mechanism.
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