{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T04:26:40Z","timestamp":1788323200113,"version":"build-2803163510"},"reference-count":84,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,11,26]],"date-time":"2020-11-26T00:00:00Z","timestamp":1606348800000},"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\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DC002368"],"award-info":[{"award-number":["R01DC002368"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000703","name":"Action on Hearing Loss","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000703","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2021,2]]},"abstract":"Key points<\/jats:title>\nMechanoelectrical transduction at auditory hair cells requires highly specialized stereociliary bundles that project from their apical surface, forming a characteristic graded \u2018staircase\u2019 structure.<\/jats:p><\/jats:list-item>\nThe morphogenesis and maintenance of these stereociliary bundles is a tightly regulated process requiring the involvement of several actin\u2010binding proteins, many of which are still unidentified.<\/jats:p><\/jats:list-item>\nWe identify a new stereociliary protein, the I\u2010BAR protein BAIAP2L2, which localizes to the tips of the shorter transducing stereocilia in both inner and outer hair cells (IHCs and OHCs).<\/jats:p><\/jats:list-item>\nWe find that Baiap2l2<\/jats:italic> deficient mice lose their second and third rows of stereocilia, their mechanoelectrical transducer current, and develop progressive hearing loss, becoming deaf by 8\u00a0months of age.<\/jats:p><\/jats:list-item>\nWe demonstrate that BAIAP2L2 localization to stereocilia tips is dependent on the motor protein MYO15A and its cargo EPS8.<\/jats:p><\/jats:list-item>\nWe propose that BAIAP2L2 is a new key protein required for the maintenance of the transducing stereocilia in mature cochlear hair cells.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>Abstract<\/jats:title>The transduction of sound waves into electrical signals depends upon mechanosensitive stereociliary bundles that project from the apical surface of hair cells within the cochlea. The height and width of these actin\u2010based stereocilia is tightly regulated throughout life to establish and maintain their characteristic staircase\u2010like structure, which is essential for normal mechanoelectrical transduction. Here, we show that BAIAP2L2, a member of the I\u2010BAR protein family, is a newly identified hair bundle protein that is localized to the tips of the shorter rows of transducing stereocilia in mouse cochlear hair cells. BAIAP2L2 was detected by immunohistochemistry from postnatal day 2.5 (P2.5) throughout adulthood. In Baiap2l2<\/jats:italic> deficient mice, outer hair cells (OHCs), but not inner hair cells (IHCs), began to lose their third row of stereocilia and showed a reduction in the size of the mechanoelectrical transducer current from just after P9. Over the following post\u2010hearing weeks, the ordered staircase structure of the bundle progressively deteriorates, such that, by 8\u00a0months of age, both OHCs and IHCs of Baiap2l2<\/jats:italic> deficient mice have lost most of the second and third rows of stereocilia and become deaf. We also found that BAIAP2L2 interacts with other key stereociliary proteins involved in normal hair bundle morphogenesis, such as CDC42, RAC1, EPS8 and ESPNL. Furthermore, we show that BAIAP2L2 localization to the stereocilia tips depends on the motor protein MYO15A and its cargo EPS8. We propose that BAIAP2L2 is key to maintenance of the normal actin structure of the transducing stereocilia in mature mouse cochlear hair cells.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp280670","type":"journal-article","created":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T15:31:32Z","timestamp":1604590292000},"page":"1173-1198","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Loss of Baiap2l2<\/i> destabilizes the transducing stereocilia of cochlear hair cells and leads to deafness"],"prefix":"10.1113","volume":"599","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1054-3901","authenticated-orcid":false,"given":"Adam J.","family":"Carlton","sequence":"first","affiliation":[{"name":"Department of Biomedical Science University of Sheffield Sheffield UK"},{"name":"Neuroscience Institute University of Sheffield Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5787-9771","authenticated-orcid":false,"given":"Julia","family":"Halford","sequence":"additional","affiliation":[{"name":"Oregon Hearing Research Center & Vollum Institute Oregon Health & Science University Portland OR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6876-861X","authenticated-orcid":false,"given":"Anna","family":"Underhill","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science University of Sheffield Sheffield UK"},{"name":"Neuroscience Institute University of Sheffield Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing\u2010Yi","family":"Jeng","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science University of Sheffield Sheffield UK"},{"name":"Neuroscience Institute University of Sheffield Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R.","family":"Avenarius","sequence":"additional","affiliation":[{"name":"Oregon Hearing Research Center & Vollum Institute Oregon Health & Science University Portland OR USA"},{"name":"Present address: Department of Pathology Wexner Medical Center The Ohio State University Columbus OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merle L.","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Oregon Hearing Research Center & Vollum Institute Oregon Health & Science University Portland OR USA"},{"name":"Present address: US Army Medical Department Activity\u2010Korea Camp Humphreys Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5366-341X","authenticated-orcid":false,"given":"Federico","family":"Ceriani","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science University of Sheffield Sheffield UK"},{"name":"Neuroscience Institute University of Sheffield Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5231-076X","authenticated-orcid":false,"given":"Kimimuepigha","family":"Ebisine","sequence":"additional","affiliation":[{"name":"Mammalian Genetics Unit MRC Harwell Institute Harwell Campus Oxfordshire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve D. 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