{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T16:54:11Z","timestamp":1769705651233,"version":"3.49.0"},"reference-count":23,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biochemistry &amp;amp; Function"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>TMEM63 is a mechanosensitive transmembrane protein implicated in calcium regulation; however, its specific function in cochlear auditory cells remains undefined. Calcium signaling is essential for cochlear hair cell proliferation, apoptosis, and migration\u2014processes fundamental to hearing preservation and potential regeneration. This research sought to examine TMEM63's regulatory function in proliferation, apoptosis, and migration within HEI\u2010OC1 cochlear hair cell systems, aimed at delineating the involvement of calcium\u2010dependent signaling pathways, particularly the CDC42\/AMPK axis. HEI\u2010OC1 cells were subjected to TMEM63 overexpression or knockdown via plasmid transfection or RNA interference. Calcium chelation was performed using BAPTA\u2010AM. Cell proliferation was assessed by CCK\u20108 screen, apoptosis via Annexin V\u2010fluorescein isothiocyanate\/propidium iodide analysis, as well as cellular cycling by flow cytometric evaluation. Wound repair combined with transwell analysis was conducted toward evaluate motility and invasiveness. Intracellular calcium levels were measured using ELISA, and signaling pathway activation was analyzed via Western blot and immunofluorescence. TMEM63 overexpression significantly promoted cell proliferation, enhanced migration, and suppressed apoptosis, while knockdown had the opposite effects. These phenotypes were reversed by BAPTA\u2010AM, indicating a calcium\u2010dependent mechanism. TMEM63 modulated intracellular Ca\u00b2\u207a levels and activated CDC42 and CaMKII while suppressing AMPK phosphorylation. Immunofluorescence confirmed consistent changes in CDC42, \u03b2\u2010catenin, AMPK, and E\u2010cadherin expression. TMEM63 regulates cochlear hair cell proliferation, apoptosis, and migration through calcium\u2010dependent activation of the CDC42\/AMPK signaling pathway. These findings highlight TMEM63 as a potential modulator of cochlear cell function and a novel target for hearing preservation strategies.<\/jats:p>","DOI":"10.1002\/cbf.70164","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T06:32:48Z","timestamp":1768977168000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Functional Characterization of TMEM63 in Cochlear Hair Cells Reveals a Role in Calcium Signaling, Proliferation, Apoptosis, and Migration"],"prefix":"10.1002","volume":"44","author":[{"given":"Peng","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurology Lishui People's Hospital of Neurology 86 Chongwen Road, Lishui District Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiankang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurology Lishui People's Hospital of Neurology 86 Chongwen Road, Lishui District Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengyu","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Neurology Lishui People's Hospital of Neurology 86 Chongwen Road, Lishui District Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongbo","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Neurology Lishui People's Hospital of Neurology 86 Chongwen Road, Lishui District Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingjing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology Lishui People's Hospital of Neurology 86 Chongwen Road, Lishui District Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2172-0502","authenticated-orcid":false,"given":"Jie","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Neurology Lishui People's Hospital of Neurology 86 Chongwen Road, Lishui District Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-021-03840-8"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232012393"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202304551"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2022.2062872"},{"issue":"11","key":"e_1_2_11_6_1","first-page":"653","article-title":"Benign Paroxysmal Positional Vertigo: Effective Diagnosis and Treatment","volume":"89","author":"Cole S. 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