0 29

Cited 0 times in

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

Authors
 Woongsu Han  ;  Jeong-Oh Shin  ;  Ji-Hyun Ma  ;  Hyehyun Min  ;  Jinsei Jung  ;  Jinu Lee  ;  Un-Kyung Kim  ;  Jae Young Choi  ;  Seok Jun Moon  ;  Dae Won Moon  ;  Jinwoong Bok  ;  Chul Hoon Kim 
Citation
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.117(20) : 11109-11117, 2020-05 
Journal Title
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 
ISSN
 0027-8424 
Issue Date
2020-05
MeSH
Acoustic Stimulation ; Animals ; Hair Cells, Auditory, Outer / cytology ; Hair Cells, Auditory, Outer / physiology* ; Hearing Loss ; Intercellular Signaling Peptides and Proteins / genetics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microtubule-Associated Proteins / genetics ; Models, Animal ; Noise* ; Otoacoustic Emissions, Spontaneous / genetics ; Otoacoustic Emissions, Spontaneous / physiology* ; Sound* ; Stereocilia / physiology ; Tectorial Membrane
Keywords
hearing loss ; outer hair cell ; stereocilia ; stereocilin ; tubby
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.
Full Text
https://www.pnas.org/content/117/20/11109.long
DOI
10.1073/pnas.1920229117
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Chul Hoon(김철훈) ORCID logo https://orcid.org/0000-0002-7360-429X
Ma, Ji Hyun(마지현) ORCID logo https://orcid.org/0000-0002-7215-9040
Moon, Seok Jun(문석준) ORCID logo https://orcid.org/0000-0001-7282-2888
Min, Hye Hyun(민혜현) ORCID logo https://orcid.org/0000-0001-5450-5088
Bok, Jin Woong(복진웅) ORCID logo https://orcid.org/0000-0003-1958-1872
Jung, Jinsei(정진세) ORCID logo https://orcid.org/0000-0003-1906-6969
Choi, Jae Young(최재영) ORCID logo https://orcid.org/0000-0001-9493-3458
Han, Woong Su(한웅수) ORCID logo https://orcid.org/0000-0002-4250-1124
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/179274
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links