Huntingtin Is Required for Epithelial Polarity through RAB11A-Mediated Apical Trafficking of PAR3-aPKC
The establishment of apical-basolateral polarity is important for both normal development and disease, for example, during tumorigenesis and metastasis. During this process, polarity complexes are targeted to the apical surface by a RAB11A-dependent mechanism. Huntingtin (HTT), the protein that is m...
Gespeichert in:
| Veröffentlicht in: | PLoS biology 2015-05, Vol.13 (5), p.e1002142-e1002142 |
|---|---|
| Hauptverfasser: | , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e1002142 |
|---|---|
| container_issue | 5 |
| container_start_page | e1002142 |
| container_title | PLoS biology |
| container_volume | 13 |
| creator | Elias, Salah McGuire, John Russel Yu, Hua Humbert, Sandrine |
| description | The establishment of apical-basolateral polarity is important for both normal development and disease, for example, during tumorigenesis and metastasis. During this process, polarity complexes are targeted to the apical surface by a RAB11A-dependent mechanism. Huntingtin (HTT), the protein that is mutated in Huntington disease, acts as a scaffold for molecular motors and promotes microtubule-based dynamics. Here, we investigated the role of HTT in apical polarity during the morphogenesis of the mouse mammary epithelium. We found that the depletion of HTT from luminal cells in vivo alters mouse ductal morphogenesis and lumen formation. HTT is required for the apical localization of PAR3-aPKC during epithelial morphogenesis in virgin, pregnant, and lactating mice. We show that HTT forms a complex with PAR3, aPKC, and RAB11A and ensures the microtubule-dependent apical vesicular translocation of PAR3-aPKC through RAB11A. We thus propose that HTT regulates polarized vesicular transport, lumen formation and mammary epithelial morphogenesis. |
| doi_str_mv | 10.1371/journal.pbio.1002142 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1685026803</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A418603629</galeid><doaj_id>oai_doaj_org_article_d81a1268e32a43f798975c771fda1f03</doaj_id><sourcerecordid>A418603629</sourcerecordid><originalsourceid>FETCH-LOGICAL-c704t-19d250ac8b8532a4bdbd1decb1e82e442cf79aedb97482d11e560aaab4774bb53</originalsourceid><addsrcrecordid>eNqVk11v0zAUhiMEYmPwDxBE4gYkUvyV2rlBCtWgFYVVZXBrOf5IXdI4s5OJ_Xvcj00r4gJkWbbs532Pj49OkjyHYAQxhe_WbvCtaEZdZd0IAoAgQQ-SU5iTPKOM5Q_v7U-SJyGsI4MKxB4nJygvCCIMnyZmOrS9bes401lIl_pqsF6r1Difnne2X-nGiiZduEZ429-k_cq7oV6ly_IDhGX2RSsr-siXnZWRu_TCGCt_RsfUmXRRLnEmFp8nT5NHRjRBPzusZ8n3j-eXk2k2v_g0m5TzTFJA-gwWCuVASFaxHCNBKlUpqLSsoGZIE4KkoYXQqiooYUhBqPMxEEJUhFJSVTk-S17ufbvGBX74osDhmOUAjRnAkZjtCeXEmnfeboS_4U5YvjtwvubC91Y2misGBYwqvX0KjpFZQXNJKTRKQLPzen-INlQbraRuey-aI9Pjm9aueO2uecwEIIqiwdu9weoP2bScc9sG7Tc8FhbjguJrGPHXh3jeXQ069Hxjg9RNI1rthl2aALIxybfOr_ZoLWImtjUuPkBucV6SyAA8RkWkRn-h4lB6Y6VrtbHx_Ejw5kgQmV7_6msxhMBn35b_wX79d_bixzFL9qz0LgSvzd3PQcC3rXFbd75tDX5ojSh7cb9Yd6LbXsC_AVWOB5E</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1680186452</pqid></control><display><type>article</type><title>Huntingtin Is Required for Epithelial Polarity through RAB11A-Mediated Apical Trafficking of PAR3-aPKC</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Public Library of Science (PLoS) Journals Open Access</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Elias, Salah ; McGuire, John Russel ; Yu, Hua ; Humbert, Sandrine</creator><contributor>Schmid, Sandra L</contributor><creatorcontrib>Elias, Salah ; McGuire, John Russel ; Yu, Hua ; Humbert, Sandrine ; Schmid, Sandra L</creatorcontrib><description>The establishment of apical-basolateral polarity is important for both normal development and disease, for example, during tumorigenesis and metastasis. During this process, polarity complexes are targeted to the apical surface by a RAB11A-dependent mechanism. Huntingtin (HTT), the protein that is mutated in Huntington disease, acts as a scaffold for molecular motors and promotes microtubule-based dynamics. Here, we investigated the role of HTT in apical polarity during the morphogenesis of the mouse mammary epithelium. We found that the depletion of HTT from luminal cells in vivo alters mouse ductal morphogenesis and lumen formation. HTT is required for the apical localization of PAR3-aPKC during epithelial morphogenesis in virgin, pregnant, and lactating mice. We show that HTT forms a complex with PAR3, aPKC, and RAB11A and ensures the microtubule-dependent apical vesicular translocation of PAR3-aPKC through RAB11A. We thus propose that HTT regulates polarized vesicular transport, lumen formation and mammary epithelial morphogenesis.</description><identifier>ISSN: 1545-7885</identifier><identifier>ISSN: 1544-9173</identifier><identifier>EISSN: 1545-7885</identifier><identifier>DOI: 10.1371/journal.pbio.1002142</identifier><identifier>PMID: 25942483</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Cell Adhesion Molecules - metabolism ; Cell division ; Cellular Biology ; Defects ; Development and progression ; Dogs ; Epithelial cells ; Epithelium - embryology ; Female ; Gene mutations ; Genetic aspects ; Health aspects ; Humans ; Huntingtin Protein ; Huntington's chorea ; Identification and classification ; Kinases ; Life Sciences ; Madin Darby Canine Kidney Cells ; Mammary Glands, Animal - embryology ; Metastasis ; Mice ; Morphogenesis ; Nerve Tissue Proteins - metabolism ; Nuclear Proteins - metabolism ; Pregnancy ; Protein Kinase C - metabolism ; Proteins ; rab GTP-Binding Proteins - metabolism ; Rodents ; Transport Vesicles - physiology</subject><ispartof>PLoS biology, 2015-05, Vol.13 (5), p.e1002142-e1002142</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>2015 Elias et al 2015 Elias et al</rights><rights>2015 Public Library of Science. 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 credited: Elias S, McGuire JR, Yu H, Humbert S (2015) Huntingtin Is Required for Epithelial Polarity through RAB11A-Mediated Apical Trafficking of PAR3-aPKC. PLoS Biol 13(5): e1002142. doi:10.1371/journal.pbio.1002142</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c704t-19d250ac8b8532a4bdbd1decb1e82e442cf79aedb97482d11e560aaab4774bb53</citedby><cites>FETCH-LOGICAL-c704t-19d250ac8b8532a4bdbd1decb1e82e442cf79aedb97482d11e560aaab4774bb53</cites><orcidid>0000-0002-9501-2658</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4420272/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4420272/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25942483$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://inserm.hal.science/inserm-02133973$$DView record in HAL$$Hfree_for_read</backlink></links><search><contributor>Schmid, Sandra L</contributor><creatorcontrib>Elias, Salah</creatorcontrib><creatorcontrib>McGuire, John Russel</creatorcontrib><creatorcontrib>Yu, Hua</creatorcontrib><creatorcontrib>Humbert, Sandrine</creatorcontrib><title>Huntingtin Is Required for Epithelial Polarity through RAB11A-Mediated Apical Trafficking of PAR3-aPKC</title><title>PLoS biology</title><addtitle>PLoS Biol</addtitle><description>The establishment of apical-basolateral polarity is important for both normal development and disease, for example, during tumorigenesis and metastasis. During this process, polarity complexes are targeted to the apical surface by a RAB11A-dependent mechanism. Huntingtin (HTT), the protein that is mutated in Huntington disease, acts as a scaffold for molecular motors and promotes microtubule-based dynamics. Here, we investigated the role of HTT in apical polarity during the morphogenesis of the mouse mammary epithelium. We found that the depletion of HTT from luminal cells in vivo alters mouse ductal morphogenesis and lumen formation. HTT is required for the apical localization of PAR3-aPKC during epithelial morphogenesis in virgin, pregnant, and lactating mice. We show that HTT forms a complex with PAR3, aPKC, and RAB11A and ensures the microtubule-dependent apical vesicular translocation of PAR3-aPKC through RAB11A. We thus propose that HTT regulates polarized vesicular transport, lumen formation and mammary epithelial morphogenesis.</description><subject>Animals</subject><subject>Cell Adhesion Molecules - metabolism</subject><subject>Cell division</subject><subject>Cellular Biology</subject><subject>Defects</subject><subject>Development and progression</subject><subject>Dogs</subject><subject>Epithelial cells</subject><subject>Epithelium - embryology</subject><subject>Female</subject><subject>Gene mutations</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Huntingtin Protein</subject><subject>Huntington's chorea</subject><subject>Identification and classification</subject><subject>Kinases</subject><subject>Life Sciences</subject><subject>Madin Darby Canine Kidney Cells</subject><subject>Mammary Glands, Animal - embryology</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Morphogenesis</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Nuclear Proteins - metabolism</subject><subject>Pregnancy</subject><subject>Protein Kinase C - metabolism</subject><subject>Proteins</subject><subject>rab GTP-Binding Proteins - metabolism</subject><subject>Rodents</subject><subject>Transport Vesicles - physiology</subject><issn>1545-7885</issn><issn>1544-9173</issn><issn>1545-7885</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNqVk11v0zAUhiMEYmPwDxBE4gYkUvyV2rlBCtWgFYVVZXBrOf5IXdI4s5OJ_Xvcj00r4gJkWbbs532Pj49OkjyHYAQxhe_WbvCtaEZdZd0IAoAgQQ-SU5iTPKOM5Q_v7U-SJyGsI4MKxB4nJygvCCIMnyZmOrS9bes401lIl_pqsF6r1Difnne2X-nGiiZduEZ429-k_cq7oV6ly_IDhGX2RSsr-siXnZWRu_TCGCt_RsfUmXRRLnEmFp8nT5NHRjRBPzusZ8n3j-eXk2k2v_g0m5TzTFJA-gwWCuVASFaxHCNBKlUpqLSsoGZIE4KkoYXQqiooYUhBqPMxEEJUhFJSVTk-S17ufbvGBX74osDhmOUAjRnAkZjtCeXEmnfeboS_4U5YvjtwvubC91Y2misGBYwqvX0KjpFZQXNJKTRKQLPzen-INlQbraRuey-aI9Pjm9aueO2uecwEIIqiwdu9weoP2bScc9sG7Tc8FhbjguJrGPHXh3jeXQ069Hxjg9RNI1rthl2aALIxybfOr_ZoLWImtjUuPkBucV6SyAA8RkWkRn-h4lB6Y6VrtbHx_Ejw5kgQmV7_6msxhMBn35b_wX79d_bixzFL9qz0LgSvzd3PQcC3rXFbd75tDX5ojSh7cb9Yd6LbXsC_AVWOB5E</recordid><startdate>20150501</startdate><enddate>20150501</enddate><creator>Elias, Salah</creator><creator>McGuire, John Russel</creator><creator>Yu, Hua</creator><creator>Humbert, Sandrine</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISN</scope><scope>ISR</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope><scope>DOA</scope><scope>CZG</scope><orcidid>https://orcid.org/0000-0002-9501-2658</orcidid></search><sort><creationdate>20150501</creationdate><title>Huntingtin Is Required for Epithelial Polarity through RAB11A-Mediated Apical Trafficking of PAR3-aPKC</title><author>Elias, Salah ; McGuire, John Russel ; Yu, Hua ; Humbert, Sandrine</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c704t-19d250ac8b8532a4bdbd1decb1e82e442cf79aedb97482d11e560aaab4774bb53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Cell Adhesion Molecules - metabolism</topic><topic>Cell division</topic><topic>Cellular Biology</topic><topic>Defects</topic><topic>Development and progression</topic><topic>Dogs</topic><topic>Epithelial cells</topic><topic>Epithelium - embryology</topic><topic>Female</topic><topic>Gene mutations</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Huntingtin Protein</topic><topic>Huntington's chorea</topic><topic>Identification and classification</topic><topic>Kinases</topic><topic>Life Sciences</topic><topic>Madin Darby Canine Kidney Cells</topic><topic>Mammary Glands, Animal - embryology</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Morphogenesis</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Nuclear Proteins - metabolism</topic><topic>Pregnancy</topic><topic>Protein Kinase C - metabolism</topic><topic>Proteins</topic><topic>rab GTP-Binding Proteins - metabolism</topic><topic>Rodents</topic><topic>Transport Vesicles - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Elias, Salah</creatorcontrib><creatorcontrib>McGuire, John Russel</creatorcontrib><creatorcontrib>Yu, Hua</creatorcontrib><creatorcontrib>Humbert, Sandrine</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><collection>PLoS Biology</collection><jtitle>PLoS biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Elias, Salah</au><au>McGuire, John Russel</au><au>Yu, Hua</au><au>Humbert, Sandrine</au><au>Schmid, Sandra L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Huntingtin Is Required for Epithelial Polarity through RAB11A-Mediated Apical Trafficking of PAR3-aPKC</atitle><jtitle>PLoS biology</jtitle><addtitle>PLoS Biol</addtitle><date>2015-05-01</date><risdate>2015</risdate><volume>13</volume><issue>5</issue><spage>e1002142</spage><epage>e1002142</epage><pages>e1002142-e1002142</pages><issn>1545-7885</issn><issn>1544-9173</issn><eissn>1545-7885</eissn><abstract>The establishment of apical-basolateral polarity is important for both normal development and disease, for example, during tumorigenesis and metastasis. During this process, polarity complexes are targeted to the apical surface by a RAB11A-dependent mechanism. Huntingtin (HTT), the protein that is mutated in Huntington disease, acts as a scaffold for molecular motors and promotes microtubule-based dynamics. Here, we investigated the role of HTT in apical polarity during the morphogenesis of the mouse mammary epithelium. We found that the depletion of HTT from luminal cells in vivo alters mouse ductal morphogenesis and lumen formation. HTT is required for the apical localization of PAR3-aPKC during epithelial morphogenesis in virgin, pregnant, and lactating mice. We show that HTT forms a complex with PAR3, aPKC, and RAB11A and ensures the microtubule-dependent apical vesicular translocation of PAR3-aPKC through RAB11A. We thus propose that HTT regulates polarized vesicular transport, lumen formation and mammary epithelial morphogenesis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25942483</pmid><doi>10.1371/journal.pbio.1002142</doi><orcidid>https://orcid.org/0000-0002-9501-2658</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1545-7885 |
| ispartof | PLoS biology, 2015-05, Vol.13 (5), p.e1002142-e1002142 |
| issn | 1545-7885 1544-9173 1545-7885 |
| language | eng |
| recordid | cdi_plos_journals_1685026803 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Animals Cell Adhesion Molecules - metabolism Cell division Cellular Biology Defects Development and progression Dogs Epithelial cells Epithelium - embryology Female Gene mutations Genetic aspects Health aspects Humans Huntingtin Protein Huntington's chorea Identification and classification Kinases Life Sciences Madin Darby Canine Kidney Cells Mammary Glands, Animal - embryology Metastasis Mice Morphogenesis Nerve Tissue Proteins - metabolism Nuclear Proteins - metabolism Pregnancy Protein Kinase C - metabolism Proteins rab GTP-Binding Proteins - metabolism Rodents Transport Vesicles - physiology |
| title | Huntingtin Is Required for Epithelial Polarity through RAB11A-Mediated Apical Trafficking of PAR3-aPKC |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-24T12%3A44%3A52IST&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=Huntingtin%20Is%20Required%20for%20Epithelial%20Polarity%20through%20RAB11A-Mediated%20Apical%20Trafficking%20of%20PAR3-aPKC&rft.jtitle=PLoS%20biology&rft.au=Elias,%20Salah&rft.date=2015-05-01&rft.volume=13&rft.issue=5&rft.spage=e1002142&rft.epage=e1002142&rft.pages=e1002142-e1002142&rft.issn=1545-7885&rft.eissn=1545-7885&rft_id=info:doi/10.1371/journal.pbio.1002142&rft_dat=%3Cgale_plos_%3EA418603629%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=1680186452&rft_id=info:pmid/25942483&rft_galeid=A418603629&rft_doaj_id=oai_doaj_org_article_d81a1268e32a43f798975c771fda1f03&rfr_iscdi=true |