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LKB1 Is Required for the Development and Maintenance of Stereocilia in Inner Ear Hair Cells in Mice

The LKB1 gene, which encodes a serine/threonine kinase, was discovered to play crucial roles in cell differentiation, proliferation, and the establishment of cell polarity. In our study, LKB1 conditional knockout mice (Atoh1-LKB1(-/-) mice) were generated to investigate LKB1 function in the inner ea...

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Autores principales: Men, Yuqin, Zhang, Aizhen, Li, Haixiang, Zhang, Tingting, Jin, Yecheng, Li, Huashun, Zhang, Jian, Gao, Jiangang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537123/
https://www.ncbi.nlm.nih.gov/pubmed/26274331
http://dx.doi.org/10.1371/journal.pone.0135841
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author Men, Yuqin
Zhang, Aizhen
Li, Haixiang
Zhang, Tingting
Jin, Yecheng
Li, Huashun
Zhang, Jian
Gao, Jiangang
author_facet Men, Yuqin
Zhang, Aizhen
Li, Haixiang
Zhang, Tingting
Jin, Yecheng
Li, Huashun
Zhang, Jian
Gao, Jiangang
author_sort Men, Yuqin
collection PubMed
description The LKB1 gene, which encodes a serine/threonine kinase, was discovered to play crucial roles in cell differentiation, proliferation, and the establishment of cell polarity. In our study, LKB1 conditional knockout mice (Atoh1-LKB1(-/-) mice) were generated to investigate LKB1 function in the inner ear. Tests of auditory brainstem response and distortion product otoacoustic emissions revealed significant decreases in the hearing sensitivities of the Atoh1-LKB1(-/-) mice. In Atoh1-LKB1(-/-) mice, malformations of hair cell stereocilliary bundles were present as early as postnatal day 1 (P1), a time long before the maturation of the hair cell bundles. In addition, we also observed outer hair cell (OHC) loss starting at P14. The impaired stereocilliary bundles occurred long before the presence of hair cell loss. Stereociliary cytoskeletal structure depends on the core actin-based cytoskeleton and several actin-binding proteins. By Western blot, we examined actin-binding proteins, specifically ERM (ezrin/radixin/moesin) proteins involved in the regulation of the actin cytoskeleton of hair cell stereocilia. Our results revealed that the phosphorylation of ERM proteins (pERM) was significantly decreased in mutant mice. Thus, we propose that the decreased pERM may be a key factor for the impaired stereocillia function, and the damaged stereocillia may induce hair cell loss and hearing impairments. Taken together, our data indicates that LKB1 is required for the development and maintenance of stereocilia in the inner ear.
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spelling pubmed-45371232015-08-20 LKB1 Is Required for the Development and Maintenance of Stereocilia in Inner Ear Hair Cells in Mice Men, Yuqin Zhang, Aizhen Li, Haixiang Zhang, Tingting Jin, Yecheng Li, Huashun Zhang, Jian Gao, Jiangang PLoS One Research Article The LKB1 gene, which encodes a serine/threonine kinase, was discovered to play crucial roles in cell differentiation, proliferation, and the establishment of cell polarity. In our study, LKB1 conditional knockout mice (Atoh1-LKB1(-/-) mice) were generated to investigate LKB1 function in the inner ear. Tests of auditory brainstem response and distortion product otoacoustic emissions revealed significant decreases in the hearing sensitivities of the Atoh1-LKB1(-/-) mice. In Atoh1-LKB1(-/-) mice, malformations of hair cell stereocilliary bundles were present as early as postnatal day 1 (P1), a time long before the maturation of the hair cell bundles. In addition, we also observed outer hair cell (OHC) loss starting at P14. The impaired stereocilliary bundles occurred long before the presence of hair cell loss. Stereociliary cytoskeletal structure depends on the core actin-based cytoskeleton and several actin-binding proteins. By Western blot, we examined actin-binding proteins, specifically ERM (ezrin/radixin/moesin) proteins involved in the regulation of the actin cytoskeleton of hair cell stereocilia. Our results revealed that the phosphorylation of ERM proteins (pERM) was significantly decreased in mutant mice. Thus, we propose that the decreased pERM may be a key factor for the impaired stereocillia function, and the damaged stereocillia may induce hair cell loss and hearing impairments. Taken together, our data indicates that LKB1 is required for the development and maintenance of stereocilia in the inner ear. Public Library of Science 2015-08-14 /pmc/articles/PMC4537123/ /pubmed/26274331 http://dx.doi.org/10.1371/journal.pone.0135841 Text en © 2015 Men et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Men, Yuqin
Zhang, Aizhen
Li, Haixiang
Zhang, Tingting
Jin, Yecheng
Li, Huashun
Zhang, Jian
Gao, Jiangang
LKB1 Is Required for the Development and Maintenance of Stereocilia in Inner Ear Hair Cells in Mice
title LKB1 Is Required for the Development and Maintenance of Stereocilia in Inner Ear Hair Cells in Mice
title_full LKB1 Is Required for the Development and Maintenance of Stereocilia in Inner Ear Hair Cells in Mice
title_fullStr LKB1 Is Required for the Development and Maintenance of Stereocilia in Inner Ear Hair Cells in Mice
title_full_unstemmed LKB1 Is Required for the Development and Maintenance of Stereocilia in Inner Ear Hair Cells in Mice
title_short LKB1 Is Required for the Development and Maintenance of Stereocilia in Inner Ear Hair Cells in Mice
title_sort lkb1 is required for the development and maintenance of stereocilia in inner ear hair cells in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537123/
https://www.ncbi.nlm.nih.gov/pubmed/26274331
http://dx.doi.org/10.1371/journal.pone.0135841
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