ArticleThe EMBO journal2015
Disruption of adaptor protein 2μ (AP-2μ) in cochlear hair cells impairs vesicle reloading of synaptic release sites and hearing.
Article in The EMBO journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 115 citations in OpenAlex.
- Two siblings with CCDC32-related cardiofacioneurodevelopmental syndrome diagnosed by clinical RNA-sequencing and review of literature.European journal of human genetics : EJHG · 2026Review
- Article
- Patterned pre-sensory spontaneous activity drives the structural refinement of developing cochlear ribbon synapses.Frontiers in synaptic neuroscience · 2026Article
- Charting the nanotopography of inner hair cell synapses using MINFLUX nanoscopy.Science advances · 2025Article
- Modeling AP2M1 developmental and epileptic encephalopathy in Drosophila.Disease models & mechanisms · 2025Article
- Structure and function of otoferlin, a synaptic protein of sensory hair cells essential for hearing.Science advances · 2025Article
- SynapseNet: Deep learning for automatic synapse reconstruction.Molecular biology of the cell · 2025Article
- Structural insights into lipid membrane binding by human ferlins.The EMBO journal · 2025Article
- Control of Synaptotagmin-1 Trafficking by SV2A-Mechanism and Consequences for Presynaptic Function and Dysfunction.Journal of neurochemistry · 2025Review
- DMXL2 Is Required for Endocytosis and Recycling of Synaptic Vesicles in Auditory Hair Cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Article
- Ca2+ binding to the C2E domain of otoferlin is required for hair cell exocytosis and hearing.Protein & cell · 2024Article
- Unraveling the molecular landscape of lead-induced cochlear synaptopathy: a quantitative proteomics analysis.Frontiers in cellular neuroscience · 2024Article
- Optical measurement of glutamate release robustly reports short-term plasticity at a fast central synapse.Frontiers in molecular neuroscience · 2024Article
- Review
- Piccolino is required for ribbon architecture at cochlear inner hair cell synapses and for hearing.EMBO reports · 2023Article
- A common variant inNational science review · 2023Article
- Probing the role of the CFrontiers in molecular neuroscience · 2023Article
- Otoferlin as a multirole CaFrontiers in cellular neuroscience · 2023Review
- Optogenetics and electron tomography for structure-function analysis of cochlear ribbon synapses.eLife · 2022Article
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Authors and funding
19 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Active zones (AZs) of inner hair cells (IHCs) indefatigably release hundreds of vesicles per second, requiring each release site to reload vesicles at tens per second. Here, we report that the endocytic adaptor protein 2μ (AP-2μ) is required for release site replenishment and hearing. We show that hair cell-specific disruption of AP-2μ slows IHC exocytosis immediately after fusion of the readily releasable pool of vesicles, despite normal abundance of membrane-proximal vesicles and intact endocytic membrane retrieval. Sound-driven postsynaptic spiking was reduced in a use-dependent manner, and the altered interspike interval statistics suggested a slowed reloading of release sites. Sustained strong stimulation led to accumulation of endosome-like vacuoles, fewer clathrin-coated endocytic intermediates, and vesicle depletion of the membrane-distal synaptic ribbon in AP-2μ-deficient IHCs, indicating a further role of AP-2μ in clathrin-dependent vesicle reformation on a timescale of many seconds. Finally, we show that AP-2 sorts its IHC-cargo otoferlin. We propose that binding of AP-2 to otoferlin facilitates replenishment of release sites, for example, via speeding AZ clearance of exocytosed material, in addition to a role of AP-2 in synaptic vesicle reformation.
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