Involvement of RhoA, ROCK I and myosin II in inverted orientation of epithelial polarity
In multicellular epithelial tissues, the orientation of polarity of each cell must be coordinated. Previously, we reported that for Madin–Darby canine kidney cells in three‐dimensional collagen gel culture, blockade of β1‐integrin by the AIIB2 antibody or expression of dominant‐negative Rac1N17 led...
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| Veröffentlicht in: | EMBO reports 2008-09, Vol.9 (9), p.923-929 |
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| creator | Yu, Wei Shewan, Annette M Brakeman, Paul Eastburn, Dennis J Datta, Anirban Bryant, David M Fan, Qi-Wen Weiss, William A Zegers, Mirjam M P Mostov, Keith E |
| description | In multicellular epithelial tissues, the orientation of polarity of each cell must be coordinated. Previously, we reported that for Madin–Darby canine kidney cells in three‐dimensional collagen gel culture, blockade of β1‐integrin by the AIIB2 antibody or expression of dominant‐negative Rac1N17 led to an inversion of polarity, such that the apical surfaces of the cells were misorientated towards the extracellular matrix. Here, we show that this process results from the activation of RhoA. Knockdown of RhoA by short hairpin RNA reverses the inverted orientation of polarity, resulting in normal cysts. Inhibition of RhoA downstream effectors, Rho kinase (ROCK I) and myosin II, has similar effects. We conclude that the RhoA–ROCK I–myosin II pathway controls the inversion of orientation of epithelial polarity caused by AIIB2 or Rac1N17. These results might be relevant to the hyperactivation of RhoA and disruption of normal polarity frequently observed in human epithelial cancers. |
| doi_str_mv | 10.1038/embor.2008.135 |
| format | Article |
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Previously, we reported that for Madin–Darby canine kidney cells in three‐dimensional collagen gel culture, blockade of β1‐integrin by the AIIB2 antibody or expression of dominant‐negative Rac1N17 led to an inversion of polarity, such that the apical surfaces of the cells were misorientated towards the extracellular matrix. Here, we show that this process results from the activation of RhoA. Knockdown of RhoA by short hairpin RNA reverses the inverted orientation of polarity, resulting in normal cysts. Inhibition of RhoA downstream effectors, Rho kinase (ROCK I) and myosin II, has similar effects. We conclude that the RhoA–ROCK I–myosin II pathway controls the inversion of orientation of epithelial polarity caused by AIIB2 or Rac1N17. These results might be relevant to the hyperactivation of RhoA and disruption of normal polarity frequently observed in human epithelial cancers.</description><identifier>ISSN: 1469-221X</identifier><identifier>EISSN: 1469-3178</identifier><identifier>EISSN: 1469-221X</identifier><identifier>DOI: 10.1038/embor.2008.135</identifier><identifier>PMID: 18660750</identifier><identifier>CODEN: ERMEAX</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Animals ; Blotting, Western ; Cell culture ; Cell Line ; Cell Polarity ; Cellular biology ; Dogs ; EMBO11 ; Epithelial Cells - cytology ; Epithelial Cells - metabolism ; epithelial polarity ; Humans ; Kidneys ; Molecular biology ; myosin II ; Myosin Type II - genetics ; Myosin Type II - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; rho-Associated Kinases - genetics ; rho-Associated Kinases - metabolism ; RhoA ; rhoA GTP-Binding Protein - genetics ; rhoA GTP-Binding Protein - metabolism ; Ribonucleic acid ; RNA ; RNA, Small Interfering - genetics ; ROCK I ; Rocks ; Scientific Report ; Transfection ; β1-integrin</subject><ispartof>EMBO reports, 2008-09, Vol.9 (9), p.923-929</ispartof><rights>European Molecular Biology Organization 2008</rights><rights>Copyright © 2008 European Molecular Biology Organization</rights><rights>Copyright Nature Publishing Group Sep 2008</rights><rights>Copyright © 2008, European Molecular Biology Organization 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6385-3a74f65b1527fdf1ad90728742ead47196da137dac88dd43ee6ed61fad2c27913</citedby><cites>FETCH-LOGICAL-c6385-3a74f65b1527fdf1ad90728742ead47196da137dac88dd43ee6ed61fad2c27913</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/PMC2529350/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2529350/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,1427,27901,27902,45550,45551,46384,46808,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18660750$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yu, Wei</creatorcontrib><creatorcontrib>Shewan, Annette M</creatorcontrib><creatorcontrib>Brakeman, Paul</creatorcontrib><creatorcontrib>Eastburn, Dennis J</creatorcontrib><creatorcontrib>Datta, Anirban</creatorcontrib><creatorcontrib>Bryant, David M</creatorcontrib><creatorcontrib>Fan, Qi-Wen</creatorcontrib><creatorcontrib>Weiss, William A</creatorcontrib><creatorcontrib>Zegers, Mirjam M P</creatorcontrib><creatorcontrib>Mostov, Keith E</creatorcontrib><title>Involvement of RhoA, ROCK I and myosin II in inverted orientation of epithelial polarity</title><title>EMBO reports</title><addtitle>EMBO Rep</addtitle><addtitle>EMBO Rep</addtitle><description>In multicellular epithelial tissues, the orientation of polarity of each cell must be coordinated. Previously, we reported that for Madin–Darby canine kidney cells in three‐dimensional collagen gel culture, blockade of β1‐integrin by the AIIB2 antibody or expression of dominant‐negative Rac1N17 led to an inversion of polarity, such that the apical surfaces of the cells were misorientated towards the extracellular matrix. Here, we show that this process results from the activation of RhoA. Knockdown of RhoA by short hairpin RNA reverses the inverted orientation of polarity, resulting in normal cysts. Inhibition of RhoA downstream effectors, Rho kinase (ROCK I) and myosin II, has similar effects. We conclude that the RhoA–ROCK I–myosin II pathway controls the inversion of orientation of epithelial polarity caused by AIIB2 or Rac1N17. These results might be relevant to the hyperactivation of RhoA and disruption of normal polarity frequently observed in human epithelial cancers.</description><subject>Animals</subject><subject>Blotting, Western</subject><subject>Cell culture</subject><subject>Cell Line</subject><subject>Cell Polarity</subject><subject>Cellular biology</subject><subject>Dogs</subject><subject>EMBO11</subject><subject>Epithelial Cells - cytology</subject><subject>Epithelial Cells - metabolism</subject><subject>epithelial polarity</subject><subject>Humans</subject><subject>Kidneys</subject><subject>Molecular biology</subject><subject>myosin II</subject><subject>Myosin Type II - genetics</subject><subject>Myosin Type II - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>rho-Associated Kinases - genetics</subject><subject>rho-Associated Kinases - metabolism</subject><subject>RhoA</subject><subject>rhoA GTP-Binding Protein - genetics</subject><subject>rhoA GTP-Binding Protein - metabolism</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Small Interfering - genetics</subject><subject>ROCK I</subject><subject>Rocks</subject><subject>Scientific Report</subject><subject>Transfection</subject><subject>β1-integrin</subject><issn>1469-221X</issn><issn>1469-3178</issn><issn>1469-221X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkc1v0zAAxSMEYmNw5YgsDpxI54_464K0VWOEjU2qgO1mubGzeiR2sdNC_3tcUm2AhHbxh_x7z89-RfESwQmCRBzafh7iBEMoJojQR8U-qpgsCeLi8W6NMbreK56ldAshpJKLp8UeEoxBTuF-cV37dejWtrd-AKEFs0U4egtml9MzUAPtDeg3ITkP6hrk0fm1jYM1IESXBXpwwW9VdumGhe2c7sAydDq6YfO8eNLqLtkXu_mg-PL-5PP0Q3l-eVpPj87LhhFBS6J51TI6RxTz1rRIGwk5FrzCVpuKI8mMRoQb3QhhTEWsZdYw1GqDG8wlIgfFu9F3uZr31jQ5VtSdWkbX67hRQTv194l3C3UT1gpTLAmF2eDNziCG7yubBtW71Niu096GVVJMVpJCwR8EkawE4qzK4Ot_wNuwij7_gsJQ5IdKyDI0GaEmhpSibe8iI6i21arf1apttSpXmwWv_nzoPb7rMgN8BH64zm4esFMnn45n281ofTgqUxb5GxvvA_83TDkqXBrsz7u7dPymGCecqquLU0XQ1ZRcfPyqzsgvavnQQg</recordid><startdate>200809</startdate><enddate>200809</enddate><creator>Yu, Wei</creator><creator>Shewan, Annette M</creator><creator>Brakeman, Paul</creator><creator>Eastburn, Dennis J</creator><creator>Datta, Anirban</creator><creator>Bryant, David M</creator><creator>Fan, Qi-Wen</creator><creator>Weiss, William A</creator><creator>Zegers, Mirjam M P</creator><creator>Mostov, Keith E</creator><general>John Wiley & Sons, Ltd</general><general>Nature Publishing Group UK</general><general>Springer Nature B.V</general><general>Nature Publishing Group</general><scope>BSCLL</scope><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>3V.</scope><scope>7QL</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>200809</creationdate><title>Involvement of RhoA, ROCK I and myosin II in inverted orientation of epithelial polarity</title><author>Yu, Wei ; Shewan, Annette M ; Brakeman, Paul ; Eastburn, Dennis J ; Datta, Anirban ; Bryant, David M ; Fan, Qi-Wen ; Weiss, William A ; Zegers, Mirjam M P ; Mostov, Keith E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6385-3a74f65b1527fdf1ad90728742ead47196da137dac88dd43ee6ed61fad2c27913</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Blotting, Western</topic><topic>Cell culture</topic><topic>Cell Line</topic><topic>Cell Polarity</topic><topic>Cellular biology</topic><topic>Dogs</topic><topic>EMBO11</topic><topic>Epithelial Cells - cytology</topic><topic>Epithelial Cells - metabolism</topic><topic>epithelial polarity</topic><topic>Humans</topic><topic>Kidneys</topic><topic>Molecular biology</topic><topic>myosin II</topic><topic>Myosin Type II - genetics</topic><topic>Myosin Type II - metabolism</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>rho-Associated Kinases - genetics</topic><topic>rho-Associated Kinases - metabolism</topic><topic>RhoA</topic><topic>rhoA GTP-Binding Protein - genetics</topic><topic>rhoA GTP-Binding Protein - metabolism</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA, Small Interfering - genetics</topic><topic>ROCK I</topic><topic>Rocks</topic><topic>Scientific Report</topic><topic>Transfection</topic><topic>β1-integrin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yu, Wei</creatorcontrib><creatorcontrib>Shewan, Annette M</creatorcontrib><creatorcontrib>Brakeman, Paul</creatorcontrib><creatorcontrib>Eastburn, Dennis J</creatorcontrib><creatorcontrib>Datta, Anirban</creatorcontrib><creatorcontrib>Bryant, David M</creatorcontrib><creatorcontrib>Fan, Qi-Wen</creatorcontrib><creatorcontrib>Weiss, William A</creatorcontrib><creatorcontrib>Zegers, Mirjam M P</creatorcontrib><creatorcontrib>Mostov, Keith E</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>EMBO reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yu, Wei</au><au>Shewan, Annette M</au><au>Brakeman, Paul</au><au>Eastburn, Dennis J</au><au>Datta, Anirban</au><au>Bryant, David M</au><au>Fan, Qi-Wen</au><au>Weiss, William A</au><au>Zegers, Mirjam M P</au><au>Mostov, Keith E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Involvement of RhoA, ROCK I and myosin II in inverted orientation of epithelial polarity</atitle><jtitle>EMBO reports</jtitle><stitle>EMBO Rep</stitle><addtitle>EMBO Rep</addtitle><date>2008-09</date><risdate>2008</risdate><volume>9</volume><issue>9</issue><spage>923</spage><epage>929</epage><pages>923-929</pages><issn>1469-221X</issn><eissn>1469-3178</eissn><eissn>1469-221X</eissn><coden>ERMEAX</coden><abstract>In multicellular epithelial tissues, the orientation of polarity of each cell must be coordinated. Previously, we reported that for Madin–Darby canine kidney cells in three‐dimensional collagen gel culture, blockade of β1‐integrin by the AIIB2 antibody or expression of dominant‐negative Rac1N17 led to an inversion of polarity, such that the apical surfaces of the cells were misorientated towards the extracellular matrix. Here, we show that this process results from the activation of RhoA. Knockdown of RhoA by short hairpin RNA reverses the inverted orientation of polarity, resulting in normal cysts. Inhibition of RhoA downstream effectors, Rho kinase (ROCK I) and myosin II, has similar effects. We conclude that the RhoA–ROCK I–myosin II pathway controls the inversion of orientation of epithelial polarity caused by AIIB2 or Rac1N17. These results might be relevant to the hyperactivation of RhoA and disruption of normal polarity frequently observed in human epithelial cancers.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>18660750</pmid><doi>10.1038/embor.2008.135</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Blotting, Western Cell culture Cell Line Cell Polarity Cellular biology Dogs EMBO11 Epithelial Cells - cytology Epithelial Cells - metabolism epithelial polarity Humans Kidneys Molecular biology myosin II Myosin Type II - genetics Myosin Type II - metabolism Reverse Transcriptase Polymerase Chain Reaction rho-Associated Kinases - genetics rho-Associated Kinases - metabolism RhoA rhoA GTP-Binding Protein - genetics rhoA GTP-Binding Protein - metabolism Ribonucleic acid RNA RNA, Small Interfering - genetics ROCK I Rocks Scientific Report Transfection β1-integrin |
| title | Involvement of RhoA, ROCK I and myosin II in inverted orientation of epithelial polarity |
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