Carrott, L;
Bowl, MR;
Aguilar, C;
Johnson, SL;
Chessum, L;
West, M;
Morse, S;
... Brown, SDM; + view all
(2016)
Absence of Neuroplastin-65 Affects Synaptogenesis in Mouse Inner Hair Cells and Causes Profound Hearing Loss.
Journal of Neuroscience
, 36
(1)
pp. 222-234.
10.1523/JNEUROSCI.1808-15.2016.
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Absence of Neuroplastin-65 Affects Synaptogenesis in Mouse Inner Hair Cells and Causes Profound Hearing Loss.pdf - Published Version Download (2MB) | Preview |
Abstract
The Neuroplastin gene encodes two synapse-enriched protein isoforms, Np55 and Np65, which are transmembrane glycoproteins that regulate several cellular processes, including the genesis, maintenance, and plasticity of synapses. We found that an absence of Np65 causes early-onset sensorineural hearing loss and prevented the normal synaptogenesis in inner hair cells (IHCs) in the newly identified mouse mutant pitch. In wild-type mice, Np65 is strongly upregulated in the cochlea from around postnatal day 12 (P12), which corresponds to the onset of hearing. Np65 was specifically localized at the presynaptic region of IHCs. We found that the colocalization of presynaptic IHC ribbons and postsynaptic afferent terminals is greatly reduced in pitch mutants. Moreover, IHC exocytosis is also reduced with mutant mice showing lower rates of vesicle release. Np65 appears to have a nonessential role in vision. We propose that Np65, by regulating IHC synaptogenesis, is critical for auditory function in mammals.
| Type: | Article |
|---|---|
| Title: | Absence of Neuroplastin-65 Affects Synaptogenesis in Mouse Inner Hair Cells and Causes Profound Hearing Loss |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1523/JNEUROSCI.1808-15.2016 |
| Publisher version: | https://doi.org/10.1523/JNEUROSCI.1808-15.2016 |
| Language: | English |
| Additional information: | This is an Open Access article distributed under the terms of the Creative Commons Attribution License Creative Commons Attribution 4.0 International, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. https://creativecommons.org/licenses/by/4.0 |
| Keywords: | exocytosis; hearing loss; inner hair cell; neuroplastin; ribbon synapse; synaptogenesis |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > The Ear Institute |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10112367 |
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