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 syna...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(Rimbp^(2-/-)),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.展开更多
基金supported by grants from the National Key R&D Program of China(2021YFA1101300,2021YFA1101800,2020YFA0112503,and 2024YFC2511103)the National Natural Science Foundation of China(82330033,82030029,82401375,81970882,92149304,and 81970883)+7 种基金the Natural Science Foundation of Jiangsu Province(BK20232007)the Science and Technology Department of Sichuan Province(2021YFS0371)Shenzhen Fundamental Research Program(JCYJ20210324125608022)the Open Project Fund of Guangdong Academy of Medical Sciences(YKY-KF202201)Beijing Natural Science Foundation(Z200019)the Jiangsu Provincial Scientific Research Center of Applied Mathematics(BK20233002)the China Postdoctoral Science Foundation(2023TQ0056,2023M730575,and GZC20230435)Jiangsu Funding Program for Excellent Postdoctoral Talent(2023ZB822).
文摘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(Rimbp^(2-/-)),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.
