DMXL2 is required for endocytosis and recycling of synaptic vesicles in auditory hair cells
Year: 2024
Type: article
Abstract: Ribbon synapses of inner hair cells are uniquely designed for ultrafast and indefatigable neurotransmission of the sound. The molecular machinery ensuring the efficient, compensatory recycling of the synaptic vesicles, however, remains elusive. This study showed that hair cell knockout of murineDmxl2, whose human homolog is responsible for non-syndromic 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 inner hair cells revealed deficiency in sustained synaptic exocytosis and endocytic membrane retrieval. Consistent with the electrophysiological findings, 3D electron microscopy reconstruction showed reduced reserve pool of synaptic vesicles 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 synaptic vesicles. Significance StatementThe molecular basis underlying efficient recycling of the ribbon synaptic vesicles in cochlear hair cells remains elusive. In this study, investigation of a hair cell-specific knockout mouse for Dmxl2 identifies its import roles in endocytosis and recycling of the auditory synaptic vesicles. The mutant mice display auditory synaptopathy, a common feature for noise-induced hearing loss and age-related hearing loss. The inner hair cells show deficiency in sustained synaptic exocytosis and endocytic membrane retrieval with reduced reserve pool of synaptic vesicles and endocytic compartments. Our results provide new insights into the molecular machinery ensuring ultrafast and indefatigable neurotransmission of the sound.
Source: Journal of Neuroscience
Authors: Hu Peng, Longhao Wang, Yunge Gao, Huihui Liu, Guotong Lin, Yu Kong, Pengcheng Xu, Hongchao Liu, Qingyue Yuan, Huanhai Liu, Lei Song, Tao Yang, Hao Wu
Institutions: Second Military Medical University, Shanghai Jiao Tong University, Shanghai Ninth People's Hospital, Shanghai Changzheng Hospital, Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Chinese Academy of Sciences, Center for Excellence in Brain Science and Intelligence Technology
Language: English
Subfield: Sensory Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W4401607379