DMXL2 is required for endocytosis and recycling of synaptic vesicles in auditory hair cells
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 <i>Dmxl2</i>, 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.
Authors
- Qingyue Yuan (ORCID: https://orcid.org/0009-0002-6775-5080)
- Huanhai Liu (ORCID: https://orcid.org/0000-0001-9756-7588)
- Guotong Lin
- Pengcheng Xu (ORCID: https://orcid.org/0000-0001-8651-208X)
- Hongchao Liu (ORCID: https://orcid.org/0000-0001-7092-9606)
- Huihui Liu (ORCID: https://orcid.org/0000-0002-2854-2480)
- Yunge Gao (ORCID: https://orcid.org/0000-0002-4336-7131)
- Lei Song (ORCID: https://orcid.org/0000-0001-5890-1774)
- Yu Xiang George Kong (ORCID: https://orcid.org/0000-0002-4441-0648)
- Hu Peng
- Longhao Wang (ORCID: https://orcid.org/0009-0008-9419-2010)
- Hao Wu (ORCID: https://orcid.org/0009-0000-1030-9819)
- Tao Yang (ORCID: https://orcid.org/0000-0002-6609-8982)
Institutions
- Shanghai Jiao Tong University (CN)
- Chinese Academy of Sciences (CN)
- Shanghai Ninth People's Hospital (CN)
- Center for Excellence in Brain Science and Intelligence Technology (CN)
- Shanghai Changzheng Hospital (CN)
Publication Details
- Journal
- Journal of Neuroscience
- Published
- 2024-08-15
- DOI
- https://doi.org/10.1523/jneurosci.1405-23.2024
- Citations
- 3
- Primary Topic
- Hearing, Cochlea, Tinnitus, Genetics
- Type
- article
- Field-Weighted Citation Impact
- 1.08
Funders
- National Science Foundation
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- Science and Technology Commission of Shanghai Municipality