Temporal and spatial assembly of inner ear hair cell ankle link condensate through phase separation.

Autor: Wang H; Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, 200030, China., Du H; Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, Shandong, 266237, China.; Air Force Medical Center, PLA, Beijing, 100074, China., Ren R; Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, Shandong, 266237, China., Du T; Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China., Lin L; Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, 200030, China., Feng Z; School of Life Sciences, Fudan University, Shanghai, 200433, China., Zhao D; Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, 200030, China., Wei X; Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, 200030, China., Zhai X; Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, Shandong, 266237, China., Wang H; College of Otolaryngology, Head and Neck Surgery, Department of Audiology and Vestibular Medicine, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Medical School of Chinese PLA, 28 Fuxing Road, 100853, Beijing, China.; National Clinical Research Center for Otolaryngologic Diseases, Chinese PLA General Hospital, Medical School of Chinese PLA, 28 Fuxing Road, 100853, Beijing, China., Dong T; Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China., Sun JP; Key Laboratory Experimental Teratology of the Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China., Wu H; Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China., Xu Z; Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, Shandong, 266237, China. xuzg@sdu.edu.cn.; Shandong Provincial Collaborative Innovation Center of Cell Biology, Shandong Normal University, Jinan, Shandong, 250014, China. xuzg@sdu.edu.cn., Lu Q; Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, 200030, China. luqing67@sjtu.edu.cn.; Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. luqing67@sjtu.edu.cn.; Bio-X-Renji Hospital Research Center, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China. luqing67@sjtu.edu.cn.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Mar 24; Vol. 14 (1), pp. 1657. Date of Electronic Publication: 2023 Mar 24.
DOI: 10.1038/s41467-023-37267-5
Abstrakt: Stereocilia are actin-based cell protrusions of inner ear hair cells and are indispensable for mechanotransduction. Ankle links connect the ankle region of developing stereocilia, playing an essential role in stereocilia development. WHRN, PDZD7, ADGRV1 and USH2A have been identified to form the so-called ankle link complex (ALC); however, the detailed mechanism underlying the temporal emergence and degeneration of ankle links remains elusive. Here we show that WHRN and PDZD7 orchestrate ADGRV1 and USH2A to assemble the ALC through liquid-liquid phase separation (LLPS). Disruption of the ALC multivalency for LLPS largely abolishes the distribution of WHRN at the ankle region of stereocilia. Interestingly, high concentration of ADGRV1 inhibits LLPS, providing a potential mechanism for ALC disassembly. Moreover, certain deafness mutations of ALC genes weaken the multivalent interactions of ALC and impair LLPS. In conclusion, our study demonstrates that LLPS mediates ALC formation, providing essential clues for understanding the pathogenesis of deafness.
(© 2023. The Author(s).)
Databáze: MEDLINE
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