GRXCR2 Regulates Taperin Localization Critical for Stereocilia Morphology and Hearing
Mutations in human GRXCR2, which encodes a protein of undetermined function, cause hearing loss by unknown mechanisms. We found that mouse GRXCR2 localizes to the base of the stereocilia, which are actin-based mechanosensing organelles in cochlear hair cells that convert sound-induced vibrations int...
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| Veröffentlicht in: | Cell reports (Cambridge) 2018-10, Vol.25 (5), p.1268-1280.e4 |
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| creator | Liu, Chang Luo, Na Tung, Chun-Yu Perrin, Benjamin J Zhao, Bo |
| description | Mutations in human GRXCR2, which encodes a protein of undetermined function, cause hearing loss by unknown mechanisms. We found that mouse GRXCR2 localizes to the base of the stereocilia, which are actin-based mechanosensing organelles in cochlear hair cells that convert sound-induced vibrations into electrical signals. The stereocilia base also contains taperin, another protein of unknown function required for human hearing. We show that taperin and GRXCR2 form a complex and that taperin is diffused throughout the stereocilia length in Grxcr2-deficient hair cells. Stereocilia lacking GRXCR2 are longer than normal and disorganized due to the mislocalization of taperin, which could modulate the actin cytoskeleton in stereocilia. Remarkably, reducing taperin expression levels could rescue the morphological defects of stereocilia and restore the hearing of Grxcr2-deficient mice. Thus, our findings suggest that GRXCR2 is critical for the morphogenesis of stereocilia and auditory perception by restricting taperin to the stereocilia base. |
| doi_str_mv | 10.1016/j.celrep.2018.09.063 |
| format | Article |
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We found that mouse GRXCR2 localizes to the base of the stereocilia, which are actin-based mechanosensing organelles in cochlear hair cells that convert sound-induced vibrations into electrical signals. The stereocilia base also contains taperin, another protein of unknown function required for human hearing. We show that taperin and GRXCR2 form a complex and that taperin is diffused throughout the stereocilia length in Grxcr2-deficient hair cells. Stereocilia lacking GRXCR2 are longer than normal and disorganized due to the mislocalization of taperin, which could modulate the actin cytoskeleton in stereocilia. Remarkably, reducing taperin expression levels could rescue the morphological defects of stereocilia and restore the hearing of Grxcr2-deficient mice. Thus, our findings suggest that GRXCR2 is critical for the morphogenesis of stereocilia and auditory perception by restricting taperin to the stereocilia base.</description><identifier>ISSN: 2211-1247</identifier><identifier>EISSN: 2211-1247</identifier><identifier>DOI: 10.1016/j.celrep.2018.09.063</identifier><identifier>PMID: 30380417</identifier><language>eng</language><publisher>United States</publisher><subject>Actin Cytoskeleton - metabolism ; Actin Cytoskeleton - ultrastructure ; Animals ; Chlorocebus aethiops ; COS Cells ; Deafness - metabolism ; Deafness - pathology ; Deafness - physiopathology ; Evoked Potentials, Auditory, Brain Stem ; Glutaredoxins - deficiency ; Glutaredoxins - metabolism ; Hair Cells, Auditory - metabolism ; Hair Cells, Auditory - ultrastructure ; Hearing ; HEK293 Cells ; Humans ; Mice, Inbred C57BL ; Protein Binding ; Proteins - metabolism ; Stereocilia - metabolism ; Stereocilia - ultrastructure</subject><ispartof>Cell reports (Cambridge), 2018-10, Vol.25 (5), p.1268-1280.e4</ispartof><rights>Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c408t-dce5acacd4e9947ba7d021d103ce553bdd87d0dfcde8f89b1e1717f86c050f9e3</citedby><cites>FETCH-LOGICAL-c408t-dce5acacd4e9947ba7d021d103ce553bdd87d0dfcde8f89b1e1717f86c050f9e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,864,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30380417$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Chang</creatorcontrib><creatorcontrib>Luo, Na</creatorcontrib><creatorcontrib>Tung, Chun-Yu</creatorcontrib><creatorcontrib>Perrin, Benjamin J</creatorcontrib><creatorcontrib>Zhao, Bo</creatorcontrib><title>GRXCR2 Regulates Taperin Localization Critical for Stereocilia Morphology and Hearing</title><title>Cell reports (Cambridge)</title><addtitle>Cell Rep</addtitle><description>Mutations in human GRXCR2, which encodes a protein of undetermined function, cause hearing loss by unknown mechanisms. We found that mouse GRXCR2 localizes to the base of the stereocilia, which are actin-based mechanosensing organelles in cochlear hair cells that convert sound-induced vibrations into electrical signals. The stereocilia base also contains taperin, another protein of unknown function required for human hearing. We show that taperin and GRXCR2 form a complex and that taperin is diffused throughout the stereocilia length in Grxcr2-deficient hair cells. Stereocilia lacking GRXCR2 are longer than normal and disorganized due to the mislocalization of taperin, which could modulate the actin cytoskeleton in stereocilia. Remarkably, reducing taperin expression levels could rescue the morphological defects of stereocilia and restore the hearing of Grxcr2-deficient mice. Thus, our findings suggest that GRXCR2 is critical for the morphogenesis of stereocilia and auditory perception by restricting taperin to the stereocilia base.</description><subject>Actin Cytoskeleton - metabolism</subject><subject>Actin Cytoskeleton - ultrastructure</subject><subject>Animals</subject><subject>Chlorocebus aethiops</subject><subject>COS Cells</subject><subject>Deafness - metabolism</subject><subject>Deafness - pathology</subject><subject>Deafness - physiopathology</subject><subject>Evoked Potentials, Auditory, Brain Stem</subject><subject>Glutaredoxins - deficiency</subject><subject>Glutaredoxins - metabolism</subject><subject>Hair Cells, Auditory - metabolism</subject><subject>Hair Cells, Auditory - ultrastructure</subject><subject>Hearing</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Mice, Inbred C57BL</subject><subject>Protein Binding</subject><subject>Proteins - metabolism</subject><subject>Stereocilia - metabolism</subject><subject>Stereocilia - ultrastructure</subject><issn>2211-1247</issn><issn>2211-1247</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkVFLwzAQx4MoKuo3EMmjL6u5tGvaF0GGTmEizA18C2lynRldU5NOmJ_ejKnMe8ld7v7_C_kRcgksAQb5zTLR2HjsEs6gSFiZsDw9IKecAwyAZ-JwLz8hFyEsWYycAZTZMTlJWVqwDMQpmY-nb6Mpp1NcrBvVY6Az1aG3LZ04rRr7pXrrWjrytrexprXz9LVHj07bxir67Hz37hq32FDVGvqIKmoX5-SoVk3Ai5_zjMwf7mejx8HkZfw0upsMdMaKfmA0DpVW2mRYlpmolDCMgwGWxsYwrYwp4o2ptcGiLsoKEASIusg1G7K6xPSM3O58u3W1wmjX9l41svN2pfxGOmXl_05r3-XCfco8BSFgGA2ufwy8-1hj6OXKhvi1jWrRrYPkwEWZ5cAhjma7Ue1dCB7rvzXA5BaKXModFLmFIlkpI5Qou9p_4p_oF0H6DWpwjGw</recordid><startdate>20181030</startdate><enddate>20181030</enddate><creator>Liu, Chang</creator><creator>Luo, Na</creator><creator>Tung, Chun-Yu</creator><creator>Perrin, Benjamin J</creator><creator>Zhao, Bo</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20181030</creationdate><title>GRXCR2 Regulates Taperin Localization Critical for Stereocilia Morphology and Hearing</title><author>Liu, Chang ; Luo, Na ; Tung, Chun-Yu ; Perrin, Benjamin J ; Zhao, Bo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c408t-dce5acacd4e9947ba7d021d103ce553bdd87d0dfcde8f89b1e1717f86c050f9e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Actin Cytoskeleton - metabolism</topic><topic>Actin Cytoskeleton - ultrastructure</topic><topic>Animals</topic><topic>Chlorocebus aethiops</topic><topic>COS Cells</topic><topic>Deafness - metabolism</topic><topic>Deafness - pathology</topic><topic>Deafness - physiopathology</topic><topic>Evoked Potentials, Auditory, Brain Stem</topic><topic>Glutaredoxins - deficiency</topic><topic>Glutaredoxins - metabolism</topic><topic>Hair Cells, Auditory - metabolism</topic><topic>Hair Cells, Auditory - ultrastructure</topic><topic>Hearing</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Mice, Inbred C57BL</topic><topic>Protein Binding</topic><topic>Proteins - metabolism</topic><topic>Stereocilia - metabolism</topic><topic>Stereocilia - ultrastructure</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Chang</creatorcontrib><creatorcontrib>Luo, Na</creatorcontrib><creatorcontrib>Tung, Chun-Yu</creatorcontrib><creatorcontrib>Perrin, Benjamin J</creatorcontrib><creatorcontrib>Zhao, Bo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell reports (Cambridge)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Chang</au><au>Luo, Na</au><au>Tung, Chun-Yu</au><au>Perrin, Benjamin J</au><au>Zhao, Bo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>GRXCR2 Regulates Taperin Localization Critical for Stereocilia Morphology and Hearing</atitle><jtitle>Cell reports (Cambridge)</jtitle><addtitle>Cell Rep</addtitle><date>2018-10-30</date><risdate>2018</risdate><volume>25</volume><issue>5</issue><spage>1268</spage><epage>1280.e4</epage><pages>1268-1280.e4</pages><issn>2211-1247</issn><eissn>2211-1247</eissn><abstract>Mutations in human GRXCR2, which encodes a protein of undetermined function, cause hearing loss by unknown mechanisms. We found that mouse GRXCR2 localizes to the base of the stereocilia, which are actin-based mechanosensing organelles in cochlear hair cells that convert sound-induced vibrations into electrical signals. The stereocilia base also contains taperin, another protein of unknown function required for human hearing. We show that taperin and GRXCR2 form a complex and that taperin is diffused throughout the stereocilia length in Grxcr2-deficient hair cells. Stereocilia lacking GRXCR2 are longer than normal and disorganized due to the mislocalization of taperin, which could modulate the actin cytoskeleton in stereocilia. Remarkably, reducing taperin expression levels could rescue the morphological defects of stereocilia and restore the hearing of Grxcr2-deficient mice. Thus, our findings suggest that GRXCR2 is critical for the morphogenesis of stereocilia and auditory perception by restricting taperin to the stereocilia base.</abstract><cop>United States</cop><pmid>30380417</pmid><doi>10.1016/j.celrep.2018.09.063</doi><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Cell Press Free Archives; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Actin Cytoskeleton - metabolism Actin Cytoskeleton - ultrastructure Animals Chlorocebus aethiops COS Cells Deafness - metabolism Deafness - pathology Deafness - physiopathology Evoked Potentials, Auditory, Brain Stem Glutaredoxins - deficiency Glutaredoxins - metabolism Hair Cells, Auditory - metabolism Hair Cells, Auditory - ultrastructure Hearing HEK293 Cells Humans Mice, Inbred C57BL Protein Binding Proteins - metabolism Stereocilia - metabolism Stereocilia - ultrastructure |
| title | GRXCR2 Regulates Taperin Localization Critical for Stereocilia Morphology and Hearing |
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