Evidence map›Paper›PMID 39966628›Full record

ArticleCell research2025

A force-sensitive adhesion GPCR is required for equilibrioception.

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 and 17 more

Abstract read
In one paragraph

Article in Cell research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Adhesion G protein-coupled receptors.Pharmacological reviews · 2026
    Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Molecular Determinants of TMC Protein Biogenesis and Trafficking.International journal of molecular sciences · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

27 authors.

Zhao Yang *NHC 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.
Shu-Hua Zhou *NHC 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.
Qi-Yue Zhang *NHC 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.
Zhi-Chen Song *NHC 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.
Wen-Wen Liu *Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Yu Sun *Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Ming-Wei Wang *Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Xiao-Long FuMedical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China.
Kong-Kai ZhuAdvanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Ying GuanDepartment of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Jie-Yu QiState 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.
Xiao-Hui WangDepartment of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Yu-Nan SunState Key Laboratory of Vascular Homeostasis and Remodeling, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China.
Yan LuNHC 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.
Yu-Qi PingMedical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China.
Yue-Tong XiNHC 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.
Zhen-Xiao TengMedical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China.
Lei XuDepartment of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Peng XiaoNHC 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.ORCID 0000-0002-9809-3481
Zhi-Gang XuShandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Shandong University School of Life Sciences, Qingdao, Shandong, China.ORCID 0000-0003-0082-7297
Wei XiongChinese Institute for Brain Research, Beijing, China.
Wei QinSchool of Physics, State Key Laboratory of Crystal Materials, Shandong University, Jinan, Shandong, China.
Wei YangDepartment of Biophysics, and Department of Neurology of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. yangwei@zju.edu.cn.ORCID 0000-0003-3065-1843
Fan YiDepartment of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China. fanyi@sdu.edu.cn.ORCID 0000-0001-8634-9788
Ren-Jie ChaiState 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. renjiec@seu.edu.cn.ORCID 0000-0002-3885-543X
Xiao YuDepartment of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China. yuxiao@sdu.edu.cn.ORCID 0000-0003-1119-8334
Jin-Peng SunNHC 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. sunjinpeng@sdu.edu.cn.ORCID 0000-0003-3572-1580

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Hair Cells, VestibularMechanotransduction, CellularReceptors, G-Protein-CoupledAnimalsCalcium SignalingGlutamic AcidHEK293 CellsHumansMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutGlutamic AcidMembrane ProteinsReceptors, G-Protein-CoupledTMC1 protein, mouse

Identifiers

PMID39966628
PMCPMC11958651

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.