Giese, APJ;
Tang, Y-Q;
Sinha, GP;
Bowl, MR;
Goldring, AC;
Parker, A;
Freeman, MJ;
... Ahmed, ZM; + view all
(2017)
CIB2 interacts with TMC1 and TMC2 and is essential for mechanotransduction in auditory hair cells.
Nature Communications
, 8
, Article 43. 10.1038/s41467-017-00061-1.
Preview |
Text
CIB2 interacts with TMC1 and TMC2 and is essential for mechanotransduction in auditory hair cells.pdf - Published Version Download (8MB) | Preview |
Abstract
Inner ear hair cells detect sound through deflection of stereocilia, the microvilli-like projections that are arranged in rows of graded heights. Calcium and integrin-binding protein 2 is essential for hearing and localizes to stereocilia, but its exact function is unknown. Here, we have characterized two mutant mouse lines, one lacking calcium and integrin-binding protein 2 and one carrying a human deafness-related Cib2 mutation, and show that both are deaf and exhibit no mechanotransduction in auditory hair cells, despite the presence of tip links that gate the mechanotransducer channels. In addition, mechanotransducing shorter row stereocilia overgrow in hair cell bundles of both Cib2 mutants. Furthermore, we report that calcium and integrin-binding protein 2 binds to the components of the hair cell mechanotransduction complex, TMC1 and TMC2, and these interactions are disrupted by deafness-causing Cib2 mutations. We conclude that calcium and integrin-binding protein 2 is required for normal operation of the mechanotransducer channels and is involved in limiting the growth of transducing stereocilia.
| Type: | Article |
|---|---|
| Title: | CIB2 interacts with TMC1 and TMC2 and is essential for mechanotransduction in auditory hair cells |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41467-017-00061-1 |
| Publisher version: | https://doi.org/10.1038/s41467-017-00061-1 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, CHANNEL-LIKE PROTEINS, MAMMALIAN INNER-EAR, BIOCHEMICAL-CHARACTERIZATION, NONSYNDROMIC DEAFNESS, BULLFROGS SACCULUS, FAST ADAPTATION, ACTIN DYNAMICS, MYOSIN-XVA, CALCIUM, STEREOCILIA |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > The Ear Institute |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10112372 |
Archive Staff Only
 |
View Item |
