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Murine GRXCR1 Has a Different Function Than GRXCR2 in the Morphogenesis of Stereocilia
Mutations in human glutaredoxin domain-containing cysteine-rich protein 1 (GRXCR1) and its paralog GRXCR2 have been linked to hearing loss in humans. Although both GRXCR1 and GRXCR2 are required for the morphogenesis of stereocilia in cochlear hair cells, a fundamental question that remains unclear...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8333275/ https://www.ncbi.nlm.nih.gov/pubmed/34366792 http://dx.doi.org/10.3389/fncel.2021.714070 |
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author | Liu, Chang Zhao, Bo |
author_facet | Liu, Chang Zhao, Bo |
author_sort | Liu, Chang |
collection | PubMed |
description | Mutations in human glutaredoxin domain-containing cysteine-rich protein 1 (GRXCR1) and its paralog GRXCR2 have been linked to hearing loss in humans. Although both GRXCR1 and GRXCR2 are required for the morphogenesis of stereocilia in cochlear hair cells, a fundamental question that remains unclear is whether GRXCR1 and GRXCR2 have similar functions in hair cells. Previously, we found that GRXCR2 is critical for the stereocilia morphogenesis by regulating taperin localization at the base of stereocilia. Reducing taperin expression level rescues the morphological defects of stereocilia and hearing loss in Grxcr2-deficient mice. So far, functions of GRXCR1 in mammalian hair cells are still unclear. Grxcr1-deficient hair cells have very thin stereocilia with less F-actin content inside, which is different from Grxcr2-deficient hair cells. In contrast to GRXCR2, which is concentrated at the base of stereocilia, GRXCR1 is diffusely distributed throughout the stereocilia. Notably, GRXCR1 interacts with GRXCR2. In Grxcr1-deficient hair cells, the expression level of GRXCR2 and taperin is reduced. Remarkably, different from that in Grxcr2-deficient mice, reducing taperin expression level does not rescue the morphological defects of stereocilia or hearing loss in Grxcr1-deficient mice. Thus, our findings suggest that GRXCR1 has different functions than GRXCR2 during the morphogenesis of stereocilia. |
format | Online Article Text |
id | pubmed-8333275 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83332752021-08-05 Murine GRXCR1 Has a Different Function Than GRXCR2 in the Morphogenesis of Stereocilia Liu, Chang Zhao, Bo Front Cell Neurosci Cellular Neuroscience Mutations in human glutaredoxin domain-containing cysteine-rich protein 1 (GRXCR1) and its paralog GRXCR2 have been linked to hearing loss in humans. Although both GRXCR1 and GRXCR2 are required for the morphogenesis of stereocilia in cochlear hair cells, a fundamental question that remains unclear is whether GRXCR1 and GRXCR2 have similar functions in hair cells. Previously, we found that GRXCR2 is critical for the stereocilia morphogenesis by regulating taperin localization at the base of stereocilia. Reducing taperin expression level rescues the morphological defects of stereocilia and hearing loss in Grxcr2-deficient mice. So far, functions of GRXCR1 in mammalian hair cells are still unclear. Grxcr1-deficient hair cells have very thin stereocilia with less F-actin content inside, which is different from Grxcr2-deficient hair cells. In contrast to GRXCR2, which is concentrated at the base of stereocilia, GRXCR1 is diffusely distributed throughout the stereocilia. Notably, GRXCR1 interacts with GRXCR2. In Grxcr1-deficient hair cells, the expression level of GRXCR2 and taperin is reduced. Remarkably, different from that in Grxcr2-deficient mice, reducing taperin expression level does not rescue the morphological defects of stereocilia or hearing loss in Grxcr1-deficient mice. Thus, our findings suggest that GRXCR1 has different functions than GRXCR2 during the morphogenesis of stereocilia. Frontiers Media S.A. 2021-07-21 /pmc/articles/PMC8333275/ /pubmed/34366792 http://dx.doi.org/10.3389/fncel.2021.714070 Text en Copyright © 2021 Liu and Zhao. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cellular Neuroscience Liu, Chang Zhao, Bo Murine GRXCR1 Has a Different Function Than GRXCR2 in the Morphogenesis of Stereocilia |
title | Murine GRXCR1 Has a Different Function Than GRXCR2 in the Morphogenesis of Stereocilia |
title_full | Murine GRXCR1 Has a Different Function Than GRXCR2 in the Morphogenesis of Stereocilia |
title_fullStr | Murine GRXCR1 Has a Different Function Than GRXCR2 in the Morphogenesis of Stereocilia |
title_full_unstemmed | Murine GRXCR1 Has a Different Function Than GRXCR2 in the Morphogenesis of Stereocilia |
title_short | Murine GRXCR1 Has a Different Function Than GRXCR2 in the Morphogenesis of Stereocilia |
title_sort | murine grxcr1 has a different function than grxcr2 in the morphogenesis of stereocilia |
topic | Cellular Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8333275/ https://www.ncbi.nlm.nih.gov/pubmed/34366792 http://dx.doi.org/10.3389/fncel.2021.714070 |
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