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| Multifaceted role of RIMBP2 in promoting hearing in murine cochlear hair cells | |
| 2022-05-04 | |
| Status | 已发表 |
| Abstract | In peripheral, the mammalian cochlea is a remarkable sensory apparatus, owning to its outer and inner hair cells (OHCs and IHCs) that amplify and transmit auditory signals to the brain, respectively. Rab3-interacting molecular (RIM) binding protein 2 (RIMBP2) is widely expressed in receptor cells and neurons, specifically in the active zones for exocytosis of synaptic vesicles (SVs), but its exact functions in the cochlea are not very well understood. We therefore generated a Rimbp2 knockout mouse model (Rimbp2-/-), which exhibited severely impaired hearing with not only elevated hearing thresholds but also increased latencies and reduced amplitudes in the Wave I of their auditory brainstem responses (ABRs). Consistent with the threshold elevation, we found significant loss of OHCs, likely through apoptosis, in the Rimbp2-/-cochlea. Consistent with changes observed in the ABR Wave I, we found greatly reduced exocytosis, both spontaneously and upon stimulation, in Rimbp2-/-IHCs. Specifically, our patch-clamp analysis on IHCs and postsynaptic spiral ganglion neurons (SGNs) revealed not only reduced readily releasable pool (RRP) of SVs but also reduced sustained release rate, along with complete blockade of fast endocytosis, in Rimbp2-/-IHCs. Lastly, with immunostaining of whole-mounted cochleae, we found that while the number of ribbon synapses in Rimbp2-/-IHCs was unchanged, their localization moved subtly but significantly towards the basal pole of IHCs. Taken together, we uncovered an unexpected role of RIMBP2 for OHC survival and a more extensive role in promoting IHC exocytosis than previously believed. |
| Keyword | RIMBP2 hearing outer hair cell apoptosis inner hair cell ribbon synapse exocytosis spiral ganglion neuron |
| Language | 英语 |
| DOI | 10.1101/2022.05.03.490398 |
| URL | 查看原文 |
| Source Publication | bioRxiv |
| Indexed By | PPRN.PPRN |
| WOS ID | PPRN:9649622 |
| WOS Subject | Neurosciences |
| Funding Project | National Key R&D Program of China["YKK19072","SKLGE-2109","JCYJ20190814093401920","BE2019711","82030029","XDA16010303","SQ2020YFA010013"] ; Strategic Priority Research Program of the Chinese Academy of Science[81970882] ; National Natural Science Foundation of China[82071059] ; Natural Science Foundation from Jiangsu Province[82171141] |
| Document Type | 预印本 |
| Identifier | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/348589 |
| Collection | 生命科学与技术学院 |
| Corresponding Author | Chai, R.; Li, G.-l.; Li, H. |
| Affiliation | 1.Southeast Univ, Key Lab Dev Genes & Human Dis, Minist Educ, Sch Life Sciencesand Technol, Nanjing 210096, Peoples R China 2.Univ Elect Sci & Technol China, Dept Otolaryngol Head & Neck Surg, Sichuan Prov Peoples Hosp, Chengdu, Peoples R China 3.Nantong Univ, Coinnovat Ctr Neuroregenerat, Nantong 226001, Peoples R China 4.Capital Med Univ, Beijing Key Lab Neural Regenerat & Repair, Beijing 100069, Peoples R China 5.Affiliated Drum Tower Hosp Nanjing Univ Med Sch, Dept Otorhinolaryngol Head & Neck Surg, Jiangsu Prov Key Med Discipline, Nanjing 210008, Peoples R China 6.Kunming Univ Sci & Technol, Inst Primate Med Translat, State Key Lab Primate Biomed Res, Kunming 650500, Yunnan, Peoples R China 7.Soochow Univ, Affiliated Hosp First, Med Coll, Inst Cardiovasc Sci & Dept Cardiovasc Surg, Suzhou 215000, Peoples R China 8.Res Inst Otorhinolaryngol, Nanjing 210008, Peoples R China 9.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 10.Fudan Univ, Eye & ENT Hosp, ENT Inst, MOE Frontiers Ctr Brain Sci, Shanghai 200031, Peoples R China 11.Southeast Univ, Zhongda Hosp, Dept Otolaryngol Head & Neck Surg, State Key Lab Bioelect, Nanjing 210096, Peoples R China 12.Southeast Univ, Sch Life Sci & Technol, Jiangsu Prov High Tech Key Lab Biomed Res, Inst Life & Hlth, Nanjing 210096, Peoples R China |
| Recommended Citation GB/T 7714 | Chai, R.,Li, G.-l.,Li, H.,et al. Multifaceted role of RIMBP2 in promoting hearing in murine cochlear hair cells. 2022. |
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