RIMBP2在促进小鼠耳蜗毛细胞听力中的多方面作用
Multifaceted Role of RIMBP2 in Promoting Hearing in Murine Cochlear Hair Cells.
作者信息
Liao Menghui, Chen Xin, Lu Ling, Liu Qing, Guo Rongrong, Qiu Yuyang, Hu Yangnan, Zhang Yuhua, Fang Qiaojun, Zhang Panpan, Li Yige, He Shuijin, Tang Mingliang, Li Huawei, Li Geng-Lin, Chai Renjie
机构信息
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.
School of Medical Engineering, Affiliated Zhuhai People's Hospital, Beijing Institute of Technology, Zhuhai, 519088, China.
出版信息
Neurosci Bull. 2025 Aug 29. doi: 10.1007/s12264-025-01472-7.
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.
哺乳动物的耳蜗依靠外毛细胞和内毛细胞（OHCs/IHCs）进行声音放大和信号传递。Rab3相互作用分子结合蛋白2（RIMBP2）在突触活跃区的受体细胞和神经元中表达，但其在听力方面的特征仍知之甚少。因此，我们构建了一个Rimbp2基因敲除（KO）小鼠模型（Rimbp2 KO），该模型表现出严重的听力损失，听觉脑干反应I波阈值升高、潜伏期延长且振幅降低。通过凋亡导致的OHC损失与阈值升高相关。在IHCs中，膜片钳记录显示胞吐作用减少，包括易释放池减少、持续释放受损和快速内吞受阻。免疫染色显示带状突触数量未变，但KO IHCs基极的位置发生了偏移。这些发现证明了RIMBP2在OHC存活中的重要作用及其在IHC突触传递中比以前认识到的更广泛的调节功能。
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