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 ear....
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| creator | Men, Yuqin Zhang, Aizhen Li, Haixiang Zhang, Tingting Jin, Yecheng Li, Huashun Zhang, Jian Gao, Jiangang |
| 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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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0135841</identifier><identifier>PMID: 26274331</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Actin ; Animals ; Auditory system ; Basic Helix-Loop-Helix Transcription Factors - genetics ; Basic Helix-Loop-Helix Transcription Factors - metabolism ; Binding ; Brain stem ; Bundles ; Bundling ; Cell differentiation ; Core loss ; Cytoskeletal Proteins - genetics ; Cytoskeletal Proteins - metabolism ; Cytoskeleton ; Cytoskeleton - genetics ; Cytoskeleton - metabolism ; Developmental biology ; Differentiation (biology) ; Ear ; Ears & hearing ; Ethics ; Ezrin ; Hair ; Hair cells ; Hair Cells, Auditory, Inner - cytology ; Hair Cells, Auditory, Inner - metabolism ; Hearing loss ; Inner ear ; Jian Zhang ; Life sciences ; LKB1 protein ; Math1 protein ; Medicine ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Mice ; Mice, Knockout ; Microfilament Proteins - genetics ; Microfilament Proteins - metabolism ; Moesin ; Muscle proteins ; Mutation ; Neurosciences ; Otoacoustic emissions ; Phosphorylation ; Polarity ; Protein binding ; Protein-Serine-Threonine Kinases - genetics ; Protein-Serine-Threonine Kinases - metabolism ; Protein-serine/threonine kinase ; Proteins ; Radixin ; Signal transduction ; Stem cells ; Stereocilia - metabolism ; Threonine</subject><ispartof>PloS one, 2015-08, Vol.10 (8), p.e0135841-e0135841</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Men et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Men et al 2015 Men et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-1876f3b00f1150f3750b6a7aabb23abb0807cafaaf92d4b42daa7b0ef03a60cb3</citedby><cites>FETCH-LOGICAL-c692t-1876f3b00f1150f3750b6a7aabb23abb0807cafaaf92d4b42daa7b0ef03a60cb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537123/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537123/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26274331$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Men, Yuqin</creatorcontrib><creatorcontrib>Zhang, Aizhen</creatorcontrib><creatorcontrib>Li, Haixiang</creatorcontrib><creatorcontrib>Zhang, Tingting</creatorcontrib><creatorcontrib>Jin, Yecheng</creatorcontrib><creatorcontrib>Li, Huashun</creatorcontrib><creatorcontrib>Zhang, Jian</creatorcontrib><creatorcontrib>Gao, Jiangang</creatorcontrib><title>LKB1 Is Required for the Development and Maintenance of Stereocilia in Inner Ear Hair Cells in Mice</title><title>PloS one</title><addtitle>PLoS One</addtitle><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.</description><subject>Actin</subject><subject>Animals</subject><subject>Auditory system</subject><subject>Basic Helix-Loop-Helix Transcription Factors - genetics</subject><subject>Basic Helix-Loop-Helix Transcription Factors - metabolism</subject><subject>Binding</subject><subject>Brain stem</subject><subject>Bundles</subject><subject>Bundling</subject><subject>Cell differentiation</subject><subject>Core loss</subject><subject>Cytoskeletal Proteins - genetics</subject><subject>Cytoskeletal Proteins - metabolism</subject><subject>Cytoskeleton</subject><subject>Cytoskeleton - genetics</subject><subject>Cytoskeleton - metabolism</subject><subject>Developmental biology</subject><subject>Differentiation (biology)</subject><subject>Ear</subject><subject>Ears & hearing</subject><subject>Ethics</subject><subject>Ezrin</subject><subject>Hair</subject><subject>Hair cells</subject><subject>Hair Cells, Auditory, Inner - cytology</subject><subject>Hair Cells, Auditory, Inner - metabolism</subject><subject>Hearing loss</subject><subject>Inner ear</subject><subject>Jian Zhang</subject><subject>Life sciences</subject><subject>LKB1 protein</subject><subject>Math1 protein</subject><subject>Medicine</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Microfilament Proteins - genetics</subject><subject>Microfilament Proteins - metabolism</subject><subject>Moesin</subject><subject>Muscle proteins</subject><subject>Mutation</subject><subject>Neurosciences</subject><subject>Otoacoustic emissions</subject><subject>Phosphorylation</subject><subject>Polarity</subject><subject>Protein binding</subject><subject>Protein-Serine-Threonine Kinases - genetics</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Protein-serine/threonine kinase</subject><subject>Proteins</subject><subject>Radixin</subject><subject>Signal transduction</subject><subject>Stem cells</subject><subject>Stereocilia - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Men, Yuqin</au><au>Zhang, Aizhen</au><au>Li, Haixiang</au><au>Zhang, Tingting</au><au>Jin, Yecheng</au><au>Li, Huashun</au><au>Zhang, Jian</au><au>Gao, Jiangang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>LKB1 Is Required for the Development and Maintenance of Stereocilia in Inner Ear Hair Cells in Mice</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-08-14</date><risdate>2015</risdate><volume>10</volume><issue>8</issue><spage>e0135841</spage><epage>e0135841</epage><pages>e0135841-e0135841</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26274331</pmid><doi>10.1371/journal.pone.0135841</doi><oa>free_for_read</oa></addata></record> |
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| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Actin Animals Auditory system Basic Helix-Loop-Helix Transcription Factors - genetics Basic Helix-Loop-Helix Transcription Factors - metabolism Binding Brain stem Bundles Bundling Cell differentiation Core loss Cytoskeletal Proteins - genetics Cytoskeletal Proteins - metabolism Cytoskeleton Cytoskeleton - genetics Cytoskeleton - metabolism Developmental biology Differentiation (biology) Ear Ears & hearing Ethics Ezrin Hair Hair cells Hair Cells, Auditory, Inner - cytology Hair Cells, Auditory, Inner - metabolism Hearing loss Inner ear Jian Zhang Life sciences LKB1 protein Math1 protein Medicine Membrane Proteins - genetics Membrane Proteins - metabolism Mice Mice, Knockout Microfilament Proteins - genetics Microfilament Proteins - metabolism Moesin Muscle proteins Mutation Neurosciences Otoacoustic emissions Phosphorylation Polarity Protein binding Protein-Serine-Threonine Kinases - genetics Protein-Serine-Threonine Kinases - metabolism Protein-serine/threonine kinase Proteins Radixin Signal transduction Stem cells Stereocilia - metabolism Threonine |
| title | LKB1 Is Required for the Development and Maintenance of Stereocilia in Inner Ear Hair Cells in Mice |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T00%3A36%3A28IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=LKB1%20Is%20Required%20for%20the%20Development%20and%20Maintenance%20of%20Stereocilia%20in%20Inner%20Ear%20Hair%20Cells%20in%20Mice&rft.jtitle=PloS%20one&rft.au=Men,%20Yuqin&rft.date=2015-08-14&rft.volume=10&rft.issue=8&rft.spage=e0135841&rft.epage=e0135841&rft.pages=e0135841-e0135841&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0135841&rft_dat=%3Cgale_plos_%3EA425616451%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1704063060&rft_id=info:pmid/26274331&rft_galeid=A425616451&rft_doaj_id=oai_doaj_org_article_37ab2393865e499eb491a52b5a15f370&rfr_iscdi=true |