DMXL2 Is Required for Endocytosis and Recycling of Synaptic Vesicles in Auditory Hair Cells.

Autor:	Peng H; Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200023, China.; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai 200125, China.; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai 200125, China.; Department of Otolaryngology-Head and Neck Surgery, Changzheng Hospital, Naval Medical University, Shanghai 200003, China., Wang L; Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200023, China.; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai 200125, China.; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai 200125, China., Gao Y; Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200023, China.; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai 200125, China.; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai 200125, China., Liu H; Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200023, China.; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai 200125, China.; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai 200125, China., Lin G; Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200023, China.; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai 200125, China.; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai 200125, China., Kong Y; Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China., Xu P; Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200023, China.; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai 200125, China.; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai 200125, China., Liu H; Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200023, China.; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai 200125, China.; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai 200125, China., Yuan Q; Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200023, China.; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai 200125, China.; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai 200125, China., Liu H; Department of Otolaryngology-Head and Neck Surgery, Changzheng Hospital, Naval Medical University, Shanghai 200003, China., Song L; Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200023, China.; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai 200125, China.; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai 200125, China., Yang T; Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200023, China yangtfxl@sina.com wuhao@shsmu.edu.cn.; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai 200125, China.; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai 200125, China., Wu H; Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200023, China yangtfxl@sina.com wuhao@shsmu.edu.cn.; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai 200125, China.; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai 200125, China.
Jazyk:	angličtina
Zdroj:	The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2024 Sep 18; Vol. 44 (38). Date of Electronic Publication: 2024 Sep 18.
DOI:	10.1523/JNEUROSCI.1405-23.2024
Abstrakt:	Ribbon synapses of inner hair cells (IHCs) are uniquely designed for ultrafast and indefatigable neurotransmission of the sound. The molecular machinery ensuring the efficient, compensatory recycling of the synaptic vesicles (SVs), however, remains elusive. This study showed that hair cell knock-out of murine Dmxl2 , whose human homolog is responsible for nonsyndromic sensorineural hearing loss DFNA71, resulted in auditory synaptopathy by impairing synaptic endocytosis and recycling. The mutant mice in the C57BL/6J background of either sex had mild hearing loss with severely diminished wave I amplitude of the auditory brainstem response. Membrane capacitance measurements of the IHCs revealed deficiency in sustained synaptic exocytosis and endocytic membrane retrieval. Consistent with the electrophysiological findings, 3D electron microscopy reconstruction showed reduced reserve pool of SVs and endocytic compartments, while the membrane-proximal and ribbon-associated vesicles remain intact. Our results propose an important role of DMXL2 in hair cell endocytosis and recycling of the SVs. Competing Interests: The authors declare no competing financial interests. (Copyright © 2024 Peng et al.)
Databáze:	MEDLINE
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