The Cation Channel TMEM63B Is an Osmosensor Required for Hearing
Summary: Hypotonic stress causes the activation of swelling-activated nonselective cation channels (NSCCs), which leads to Ca2+-dependent regulatory volume decrease (RVD) and adaptive maintenance of the cell volume; however, the molecular identities of the osmosensitive NSCCs remain unclear. Here, w...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-05-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720305453 |
| _version_ | 1829107201062469632 |
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| author | Han Du Chang Ye Dan Wu Yan-Yu Zang Linqing Zhang Chen Chen Xue-Yan He Jian-Jun Yang Ping Hu Zhengfeng Xu Guoqiang Wan Yun Stone Shi |
| author_facet | Han Du Chang Ye Dan Wu Yan-Yu Zang Linqing Zhang Chen Chen Xue-Yan He Jian-Jun Yang Ping Hu Zhengfeng Xu Guoqiang Wan Yun Stone Shi |
| author_sort | Han Du |
| collection | DOAJ |
| description | Summary: Hypotonic stress causes the activation of swelling-activated nonselective cation channels (NSCCs), which leads to Ca2+-dependent regulatory volume decrease (RVD) and adaptive maintenance of the cell volume; however, the molecular identities of the osmosensitive NSCCs remain unclear. Here, we identified TMEM63B as an osmosensitive NSCC activated by hypotonic stress. TMEM63B is enriched in the inner ear sensory hair cells. Genetic deletion of TMEM63B results in necroptosis of outer hair cells (OHCs) and progressive hearing loss. Mechanistically, the TMEM63B channel mediates hypo-osmolarity-induced Ca2+ influx, which activates Ca2+-dependent K+ channels required for the maintenance of OHC morphology. These findings demonstrate that TMEM63B is an osmosensor of the mammalian inner ear and the long-sought cation channel mediating Ca2+-dependent RVD. |
| first_indexed | 2024-12-12T06:33:55Z |
| format | Article |
| id | doaj.art-45d710199b274114bdc65f57fb41701a |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-12T06:33:55Z |
| publishDate | 2020-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-45d710199b274114bdc65f57fb41701a2022-12-22T00:34:30ZengElsevierCell Reports2211-12472020-05-01315The Cation Channel TMEM63B Is an Osmosensor Required for HearingHan Du0Chang Ye1Dan Wu2Yan-Yu Zang3Linqing Zhang4Chen Chen5Xue-Yan He6Jian-Jun Yang7Ping Hu8Zhengfeng Xu9Guoqiang Wan10Yun Stone Shi11State Key Laboratory of Pharmaceutical Biotechnology, Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing University, Nanjing 210032, China; Ministry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210032, ChinaState Key Laboratory of Pharmaceutical Biotechnology, Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing University, Nanjing 210032, China; Ministry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210032, ChinaState Key Laboratory of Pharmaceutical Biotechnology, Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing University, Nanjing 210032, China; Ministry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210032, ChinaState Key Laboratory of Pharmaceutical Biotechnology, Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing University, Nanjing 210032, China; Ministry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210032, ChinaMinistry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210032, ChinaMinistry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210032, ChinaMinistry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210032, ChinaDepartment of Anesthesiology and Perioperative Medicine, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province 450052, ChinaDepartment of Prenatal Diagnosis, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Healthcare Hospital, Nanjing 210004, ChinaDepartment of Prenatal Diagnosis, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Healthcare Hospital, Nanjing 210004, ChinaMinistry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210032, China; Institute for Brain Sciences, Nanjing University, Nanjing 210032, China; Corresponding authorState Key Laboratory of Pharmaceutical Biotechnology, Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing University, Nanjing 210032, China; Ministry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210032, China; Institute for Brain Sciences, Nanjing University, Nanjing 210032, China; Chemistry and Biomedicine Innovation Center, Nanjing University, Nanjing 210032, China; Corresponding authorSummary: Hypotonic stress causes the activation of swelling-activated nonselective cation channels (NSCCs), which leads to Ca2+-dependent regulatory volume decrease (RVD) and adaptive maintenance of the cell volume; however, the molecular identities of the osmosensitive NSCCs remain unclear. Here, we identified TMEM63B as an osmosensitive NSCC activated by hypotonic stress. TMEM63B is enriched in the inner ear sensory hair cells. Genetic deletion of TMEM63B results in necroptosis of outer hair cells (OHCs) and progressive hearing loss. Mechanistically, the TMEM63B channel mediates hypo-osmolarity-induced Ca2+ influx, which activates Ca2+-dependent K+ channels required for the maintenance of OHC morphology. These findings demonstrate that TMEM63B is an osmosensor of the mammalian inner ear and the long-sought cation channel mediating Ca2+-dependent RVD.http://www.sciencedirect.com/science/article/pii/S2211124720305453osmosensorTMEM63BTMEM63ATMEM63COSCA1hair cells |
| spellingShingle | Han Du Chang Ye Dan Wu Yan-Yu Zang Linqing Zhang Chen Chen Xue-Yan He Jian-Jun Yang Ping Hu Zhengfeng Xu Guoqiang Wan Yun Stone Shi The Cation Channel TMEM63B Is an Osmosensor Required for Hearing Cell Reports osmosensor TMEM63B TMEM63A TMEM63C OSCA1 hair cells |
| title | The Cation Channel TMEM63B Is an Osmosensor Required for Hearing |
| title_full | The Cation Channel TMEM63B Is an Osmosensor Required for Hearing |
| title_fullStr | The Cation Channel TMEM63B Is an Osmosensor Required for Hearing |
| title_full_unstemmed | The Cation Channel TMEM63B Is an Osmosensor Required for Hearing |
| title_short | The Cation Channel TMEM63B Is an Osmosensor Required for Hearing |
| title_sort | cation channel tmem63b is an osmosensor required for hearing |
| topic | osmosensor TMEM63B TMEM63A TMEM63C OSCA1 hair cells |
| url | http://www.sciencedirect.com/science/article/pii/S2211124720305453 |
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