{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T09:43:37Z","timestamp":1788342217486,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.pgen.1009937","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T00:00:00Z","timestamp":1644451200000}}],"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T00:00:00Z","timestamp":1643587200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/S006257\/1"],"award-info":[{"award-number":["BB\/S006257\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UP_1503\/2"],"award-info":[{"award-number":["MC_UP_1503\/2"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000703","name":"Action on Hearing Loss","doi-asserted-by":"publisher","award":["G81"],"award-info":[{"award-number":["G81"]}],"id":[{"id":"10.13039\/501100000703","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    Mammalian hearing involves the mechanoelectrical transduction (MET) of sound-induced fluid waves in the cochlea. Essential to this process are the specialised sensory cochlear cells, the inner (IHCs) and outer hair cells (OHCs). While genetic hearing loss is highly heterogeneous, understanding the requirement of each gene will lead to a better understanding of the molecular basis of hearing and also to therapeutic opportunities for deafness. The\n                    <jats:italic>Neuroplastin<\/jats:italic>\n                    (\n                    <jats:italic>Nptn<\/jats:italic>\n                    ) gene, which encodes two protein isoforms Np55 and Np65, is required for hearing, and homozygous loss-of-function mutations that affect both isoforms lead to profound deafness in mice. Here we have utilised several distinct mouse models to elaborate upon the spatial, temporal, and functional requirement of\n                    <jats:italic>Nptn<\/jats:italic>\n                    for hearing. While we demonstrate that both Np55 and Np65 are present in cochlear cells, characterisation of a Np65-specific mouse knockout shows normal hearing thresholds indicating that Np65 is functionally redundant for hearing. In contrast, we find that\n                    <jats:italic>Nptn<\/jats:italic>\n                    -knockout mice have significantly reduced maximal MET currents and MET channel open probabilities in mature OHCs, with both OHCs and IHCs also failing to develop fully mature basolateral currents. Furthermore, comparing the hearing thresholds and IHC synapse structure of\n                    <jats:italic>Nptn-<\/jats:italic>\n                    knockout mice with those of mice that lack\n                    <jats:italic>Nptn<\/jats:italic>\n                    only in IHCs and OHCs shows that the majority of the auditory deficit is explained by hair cell dysfunction, with abnormal afferent synapses contributing only a small proportion of the hearing loss. Finally, we show that continued expression of Neuroplastin in OHCs of adult mice is required for membrane localisation of Plasma Membrane Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ATPase 2 (PMCA2), which is essential for hearing function. Moreover,\n                    <jats:italic>Nptn<\/jats:italic>\n                    haploinsufficiency phenocopies\n                    <jats:italic>Atp2b2<\/jats:italic>\n                    (encodes PMCA2) mutations, with heterozygous\n                    <jats:italic>Nptn<\/jats:italic>\n                    -knockout mice exhibiting hearing loss through genetic interaction with the\n                    <jats:italic>Cdh23<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>ahl<\/jats:italic>\n                    <\/jats:sup>\n                    allele. Together, our findings provide further insight to the functional requirement of\n                    <jats:italic>Neuroplastin<\/jats:italic>\n                    for mammalian hearing.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1009937","type":"journal-article","created":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T13:39:50Z","timestamp":1643636390000},"page":"e1009937","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Neuroplastin genetically interacts with Cadherin 23 and the encoded isoform Np55 is sufficient for cochlear hair cell function and hearing"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8210-3526","authenticated-orcid":true,"given":"Sherylanne","family":"Newton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3029-5500","authenticated-orcid":true,"given":"Fanbo","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1054-3901","authenticated-orcid":true,"given":"Adam J.","family":"Carlton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4655-1778","authenticated-orcid":true,"given":"Carlos","family":"Aguilar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Parker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma F.","family":"Codner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia","family":"Teboul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0572-0600","authenticated-orcid":true,"given":"Sara","family":"Wells","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve D. M.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8770-7628","authenticated-orcid":true,"given":"Walter","family":"Marcotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7971-445X","authenticated-orcid":true,"given":"Michael R.","family":"Bowl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,1,31]]},"reference":[{"issue":"20","key":"pgen.1009937.ref001","doi-asserted-by":"crossref","first-page":"8261","DOI":"10.1523\/JNEUROSCI.18-20-08261.1998","article-title":"The endogenous calcium buffer and the time course of transducer adaptation in auditory hair cells","volume":"18","author":"AJ Ricci","year":"1998","journal-title":"J 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