Multifaceted Role of RIMBP2 in Promoting Hearing in Murine Cochlear Hair Cells

Menghui Liao^{1

2

3}, Xin Chen¹, Ling Lu¹, Qing Liu¹, Rongrong Guo^{4

5}, Yuyang Qiu¹, Yangnan Hu¹, Yuhua Zhang¹, Qiaojun Fang¹, Panpan Zhang¹, Yige Li¹, Shuijin He⁶, Mingliang Tang⁷, Huawei Li⁸, Geng-Lin Li⁹, Renjie Chai^{10

11

12

13

14}

Affiliations

¹ Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, State Key Laboratory of Digital Medical Engineering, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Southeast University, Nanjing, 210096, China.
² School of Medical Engineering, Affiliated Zhuhai People's Hospital, Beijing Institute of Technology, Zhuhai, 519088, China.
³ Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, China.
⁴ State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, Yunnan, China.
⁵ Institute for Cardiovascular Science & Department of Cardiovascular Surgery of the First Affiliated Hospital, Medical College, Soochow University, Suzhou, 215000, China.
⁶ School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.
⁷ Institute for Cardiovascular Science & Department of Cardiovascular Surgery of the First Affiliated Hospital, Medical College, Soochow University, Suzhou, 215000, China. mltang@suda.edu.cn.
⁸ ENT Institute and Department of Otorhinolaryngology, Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 200031, China. hwli@shmu.edu.cn.
⁹ ENT Institute and Department of Otorhinolaryngology, Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 200031, China. genglin.li@fdeent.org.
¹⁰ Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, State Key Laboratory of Digital Medical Engineering, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Southeast University, Nanjing, 210096, China. renjiec@seu.edu.cn.
¹¹ Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, China. renjiec@seu.edu.cn.
¹² Department of Neurology, Aerospace Center Hospital, School of Life Science, Beijing Institute of Technology, Beijing, 100081, China. renjiec@seu.edu.cn.
¹³ Department of Otolaryngology Head and Neck Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, China. renjiec@seu.edu.cn.
¹⁴ Southeast University Shenzhen Research Institute, Shenzhen, 518063, China. renjiec@seu.edu.cn.

PMID: 40880039
DOI: 10.1007/s12264-025-01472-7

Multifaceted Role of RIMBP2 in Promoting Hearing in Murine Cochlear Hair Cells

Menghui Liao et al. Neurosci Bull. 2025.

. 2025 Aug 29.

doi: 10.1007/s12264-025-01472-7. Online ahead of print.

Authors

Affiliations

¹ Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, State Key Laboratory of Digital Medical Engineering, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Southeast University, Nanjing, 210096, China.
² School of Medical Engineering, Affiliated Zhuhai People's Hospital, Beijing Institute of Technology, Zhuhai, 519088, China.
³ Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, China.
⁴ State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, Yunnan, China.
⁵ Institute for Cardiovascular Science & Department of Cardiovascular Surgery of the First Affiliated Hospital, Medical College, Soochow University, Suzhou, 215000, China.
⁶ School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.
⁷ Institute for Cardiovascular Science & Department of Cardiovascular Surgery of the First Affiliated Hospital, Medical College, Soochow University, Suzhou, 215000, China. mltang@suda.edu.cn.
⁸ ENT Institute and Department of Otorhinolaryngology, Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 200031, China. hwli@shmu.edu.cn.
⁹ ENT Institute and Department of Otorhinolaryngology, Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 200031, China. genglin.li@fdeent.org.
¹⁰ Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, State Key Laboratory of Digital Medical Engineering, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Southeast University, Nanjing, 210096, China. renjiec@seu.edu.cn.
¹¹ Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, China. renjiec@seu.edu.cn.
¹² Department of Neurology, Aerospace Center Hospital, School of Life Science, Beijing Institute of Technology, Beijing, 100081, China. renjiec@seu.edu.cn.
¹³ Department of Otolaryngology Head and Neck Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, China. renjiec@seu.edu.cn.
¹⁴ Southeast University Shenzhen Research Institute, Shenzhen, 518063, China. renjiec@seu.edu.cn.

PMID: 40880039
DOI: 10.1007/s12264-025-01472-7

Abstract

The mammalian cochlea relies on outer and inner hair cells (OHCs/IHCs) for sound amplification and signal transmission. Rab3-interacting molecular binding protein 2 (RIMBP2), expressed in receptor cells and neurons at synaptic active zones, remains poorly characterized in hearing. We therefore generated a Rimbp2 knockout (KO) mouse model (Rimbp2^-/-), which exhibited severe hearing loss with elevated thresholds, prolonged latencies, and reduced amplitudes in auditory brainstem response Wave I. OHC loss via apoptosis was correlated with threshold elevation. In IHCs, patch-clamp recordings revealed reduced exocytosis, including a diminished readily-releasable pool, impaired sustained release, and blocked fast endocytosis. Immunostaining showed unchanged ribbon synapse numbers but positional shifts in the basal pole of KO IHCs. These findings demonstrated RIMBP2's essential role in OHC survival and its broader regulatory functions in IHC synaptic transmission than previously recognized.

Keywords: Apoptosis; Exocytosis; Hair cell; Hearing; RIMBP2; Ribbon synapse.

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Conflict of interest statement

Conflict of interest: The authors declare that there are no conflicts of interest.

References

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Multifaceted Role of RIMBP2 in Promoting Hearing in Murine Cochlear Hair Cells

Affiliations

Multifaceted Role of RIMBP2 in Promoting Hearing in Murine Cochlear Hair Cells

Authors

Affiliations

Abstract

Conflict of interest statement

References

LinkOut - more resources

Full Text Sources

Research Materials