During hearing, cochlear inner hair cells (IHCs) sense sound and translate it into nerve signals that can be interpreted by the brain. IHCs contain ribbon synapses, which have a high rate of sustained neurotransmitter release that is mediated by the fast exocytosis and subsequent recycling of synaptic vesicles (SVs) in the IHC active zone. Now, Carolin Wichmann, Tobias Moser and colleagues (Kroll et al., 2020) investigate the role of the neuronal endocytic adaptor protein AP180, which is known to promote SV endocytosis through clearance of vesicle release sites, at mouse IHC ribbon synapses. They show that AP180 localises most strongly to and, upon depolarisation, further accumulates at, the basal IHC plasma membrane, where ribbon synapses are found. AP180-knockout mice have modestly increased auditory brainstem response thresholds compared to those in control mice, indicating that their hearing is impaired. Moreover, the absence of AP180 causes a reduction in SVs and clathrin-coated vesicles at ribbon synapses and a decrease in the rate of SV replenishment. The authors reveal that membrane-proximal SVs in AP180-knockout mice show a greater degree of tethering to the IHC active zone after depolarisation, suggesting that SVs fail to replenish efficiently due to ineffective clearance of vesicles at the release site. Together, these findings establish AP180 as a novel regulator of hearing that facilitates the turnover of vesicles at IHC synapses to ensure continuous neurotransmitter release.
