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Distinct roles of stereociliary links in the nonlinear sound processing and noise resistance of cochlear outer hair cells

Title
Distinct roles of stereociliary links in the nonlinear sound processing and noise resistance of cochlear outer hair cells
Authors
Han, WoongsuShin, Jeong-OhMa, Ji-HyunMin, HyehyunJung, JinseiLee, JinuKim, Un-KyungChoi, Jae YoungMoon, Seok JunMoon, DaeWonBok, JinwoongKim, Chul Hoon
DGIST Authors
Han, Woongsu; Shin, Jeong-Oh; Ma, Ji-Hyun; Min, Hyehyun; Jung, Jinsei; Lee, Jinu; Kim, Un-Kyung; Choi, Jae Young; Moon, Seok Jun; Moon, DaeWon; Bok, Jinwoong; Kim, Chul Hoon
Issue Date
2020-05
Citation
Proceedings of the National Academy of Sciences of the United States of America, 117(20), 11109-11117
Type
Article
Article Type
Article
Author Keywords
hearing lossouter hair cellstereociliatubbystereocilin
Keywords
TECTORIAL MEMBRANETUBBY PROTEINSBUNDLEGENETRAFFICKINGMUTATIONSHOMOLOGYMODELSMICEFAT
ISSN
0027-8424
Abstract
Outer hair cells (OHCs) play an essential role in hearing by acting as a nonlinear amplifier which helps the cochlea detect sounds with high sensitivity and accuracy. This nonlinear sound processing generates distortion products, which can be measured as distortion-product otoacoustic emissions (DPOAEs). The OHC stereocilia that respond to sound vibrations are connected by three kinds of extracellular links: tip links that connect the taller stereocilia to shorter ones and convey force to the mechanoelectrical transduction channels, tectorial membrane-attachment crowns (TM-ACs) that connect the tallest stereocilia to one another and to the overlying TM, and horizontal top connectors (HTCs) that link adjacent stereocilia. While the tip links have been extensively studied, the roles that the other two types of links play in hearing are much less clear, largely because of a lack of suitable animal models. Here, while analyzing genetic combinations of tubby mice, we encountered models missing both HTCs and TM-ACs or HTCs alone. We found that the tubby mutation causes loss of both HTCs and TM-ACs due to a mislocalization of stereocilin, which results in OHC dysfunction leading to severe hearing loss. Intriguingly, the addition of the modifier allele modifier of tubby hearing 1 in tubby mice selectively rescues the TM-ACs but not the HTCs. Hearing is significantly rescued in these mice with robust DPOAE production, indicating an essential role of the TM-ACs but not the HTCs in normal OHC function. In contrast, the HTCs are required for the resistance of hearing to damage caused by noise stress. © 2020 National Academy of Sciences. All rights reserved.
URI
http://hdl.handle.net/20.500.11750/12053
DOI
10.1073/pnas.1920229117
Publisher
National Academy of Sciences
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