Menghui Liao1,2,3 · Xin Chen1  · Ling Lu1  · Qing Liu1  · Rongrong Guo4,5 · Yuyang Qiu1  · Yangnan Hu1  · Yuhua Zhang1  · Qiaojun Fang1  · Panpan Zhang1  · Yige Li1  · Shuijin He6  · Mingliang Tang5  · Huawei Li7  · Geng‑Lin Li7  · Renjie Chai1,3,8,9,10

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 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

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

RIMBP2; Hearing; Hair cell; Apoptosis; Ribbon synapse; Exocytosis

[SpringerLink]