Complete Polarization of Single Intestinal Epithelial Cells upon Activation of LKB1 by STRAD
The LKB1 gene encodes a serine/threonine kinase that is mutated in the Peutz-Jeghers cancer syndrome. LKB1 is homologous to the Par-4 polarity genes in C. elegans and D. melanogaster. We have previously reported the identification and characterization of an LKB1-specific adaptor protein, STRAD, whic...
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| Veröffentlicht in: | Cell 2004-02, Vol.116 (3), p.457-466 |
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| creator | Baas, Annette F Kuipers, Jeroen van der Wel, Nicole N Batlle, Eduard Koerten, Henk K Peters, Peter J Clevers, Hans C |
| description | The
LKB1 gene encodes a serine/threonine kinase that is mutated in the Peutz-Jeghers cancer syndrome. LKB1 is homologous to the Par-4 polarity genes in
C. elegans and
D. melanogaster. We have previously reported the identification and characterization of an LKB1-specific adaptor protein, STRAD, which activates LKB1 and translocates it from nucleus to cytoplasm. We have now constructed intestinal epithelial cell lines in which inducible STRAD activates LKB1. Upon LKB1 activation, single cells rapidly remodel their actin cytoskeleton to form an apical brush border. The junctional proteins ZO-1 and p120 redistribute in a dotted circle peripheral to the brush border, in the absence of cell-cell contacts. Apical and basolateral markers sort to their respective membrane domains. We conclude that LKB1 can induce complete polarity in intestinal epithelial cells. In contrast to current thinking on polarization of simple epithelia, these cells can fully polarize in the absence of junctional cell-cell contacts. |
| doi_str_mv | 10.1016/S0092-8674(04)00114-X |
| format | Article |
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LKB1 gene encodes a serine/threonine kinase that is mutated in the Peutz-Jeghers cancer syndrome. LKB1 is homologous to the Par-4 polarity genes in
C. elegans and
D. melanogaster. We have previously reported the identification and characterization of an LKB1-specific adaptor protein, STRAD, which activates LKB1 and translocates it from nucleus to cytoplasm. We have now constructed intestinal epithelial cell lines in which inducible STRAD activates LKB1. Upon LKB1 activation, single cells rapidly remodel their actin cytoskeleton to form an apical brush border. The junctional proteins ZO-1 and p120 redistribute in a dotted circle peripheral to the brush border, in the absence of cell-cell contacts. Apical and basolateral markers sort to their respective membrane domains. We conclude that LKB1 can induce complete polarity in intestinal epithelial cells. In contrast to current thinking on polarization of simple epithelia, these cells can fully polarize in the absence of junctional cell-cell contacts.</description><identifier>ISSN: 0092-8674</identifier><identifier>EISSN: 1097-4172</identifier><identifier>DOI: 10.1016/S0092-8674(04)00114-X</identifier><identifier>PMID: 15016379</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Actin Cytoskeleton - metabolism ; Actin Cytoskeleton - ultrastructure ; Adaptor Proteins, Vesicular Transport - genetics ; Adaptor Proteins, Vesicular Transport - metabolism ; Caco-2 Cells ; Cell Communication - genetics ; Cell Polarity - physiology ; Humans ; Intercellular Junctions - genetics ; Intestinal Mucosa - cytology ; Intestinal Mucosa - metabolism ; Intestinal Mucosa - ultrastructure ; Membrane Proteins - metabolism ; Microscopy, Electron ; Microvilli - metabolism ; Microvilli - ultrastructure ; p120 GTPase Activating Protein - metabolism ; Peutz-Jeghers Syndrome - genetics ; Peutz-Jeghers Syndrome - metabolism ; Phosphoproteins - metabolism ; Protein-Serine-Threonine Kinases - genetics ; Protein-Serine-Threonine Kinases - metabolism ; Zonula Occludens-1 Protein</subject><ispartof>Cell, 2004-02, Vol.116 (3), p.457-466</ispartof><rights>2004 Cell Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c557t-8befac6329df4ff9d290179b02de1c1ccac6e567d8fc498acb63dd3a17ad884b3</citedby><cites>FETCH-LOGICAL-c557t-8befac6329df4ff9d290179b02de1c1ccac6e567d8fc498acb63dd3a17ad884b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0092-8674(04)00114-X$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15016379$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Baas, Annette F</creatorcontrib><creatorcontrib>Kuipers, Jeroen</creatorcontrib><creatorcontrib>van der Wel, Nicole N</creatorcontrib><creatorcontrib>Batlle, Eduard</creatorcontrib><creatorcontrib>Koerten, Henk K</creatorcontrib><creatorcontrib>Peters, Peter J</creatorcontrib><creatorcontrib>Clevers, Hans C</creatorcontrib><title>Complete Polarization of Single Intestinal Epithelial Cells upon Activation of LKB1 by STRAD</title><title>Cell</title><addtitle>Cell</addtitle><description>The
LKB1 gene encodes a serine/threonine kinase that is mutated in the Peutz-Jeghers cancer syndrome. LKB1 is homologous to the Par-4 polarity genes in
C. elegans and
D. melanogaster. We have previously reported the identification and characterization of an LKB1-specific adaptor protein, STRAD, which activates LKB1 and translocates it from nucleus to cytoplasm. We have now constructed intestinal epithelial cell lines in which inducible STRAD activates LKB1. Upon LKB1 activation, single cells rapidly remodel their actin cytoskeleton to form an apical brush border. The junctional proteins ZO-1 and p120 redistribute in a dotted circle peripheral to the brush border, in the absence of cell-cell contacts. Apical and basolateral markers sort to their respective membrane domains. We conclude that LKB1 can induce complete polarity in intestinal epithelial cells. In contrast to current thinking on polarization of simple epithelia, these cells can fully polarize in the absence of junctional cell-cell contacts.</description><subject>Actin Cytoskeleton - metabolism</subject><subject>Actin Cytoskeleton - ultrastructure</subject><subject>Adaptor Proteins, Vesicular Transport - genetics</subject><subject>Adaptor Proteins, Vesicular Transport - metabolism</subject><subject>Caco-2 Cells</subject><subject>Cell Communication - genetics</subject><subject>Cell Polarity - physiology</subject><subject>Humans</subject><subject>Intercellular Junctions - genetics</subject><subject>Intestinal Mucosa - cytology</subject><subject>Intestinal Mucosa - metabolism</subject><subject>Intestinal Mucosa - ultrastructure</subject><subject>Membrane Proteins - metabolism</subject><subject>Microscopy, Electron</subject><subject>Microvilli - metabolism</subject><subject>Microvilli - ultrastructure</subject><subject>p120 GTPase Activating Protein - metabolism</subject><subject>Peutz-Jeghers Syndrome - genetics</subject><subject>Peutz-Jeghers Syndrome - metabolism</subject><subject>Phosphoproteins - metabolism</subject><subject>Protein-Serine-Threonine Kinases - genetics</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Zonula Occludens-1 Protein</subject><issn>0092-8674</issn><issn>1097-4172</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkNFKwzAUhoMobk4fQemV6EU1aZsmvZJZpw4HipuwCyGkyalGurY23WA-vZkb83IQSCDff_7Dh9ApwVcEk_h6jHES-Dxm0QWOLjEmJPKne6hLcML8iLBgH3W3SAcdWfuFMeaU0kPUIdSNCFnSRe9pNasLaMF7qQrZmB_Zmqr0qtwbm_KjAG9YtmBbU8rCG9Sm_YTCuGcKRWG9ee3QvmrNYpsaPd0SL1t648lr_-4YHeSysHCyuXvo7X4wSR_90fPDMO2PfEUpa32eQS5VHAaJzqM8T3SQYMKSDAcaiCJKuU-gMdM8V1HCpcriUOtQEiY151EW9tD5em7dVN9zt66YGavcirKEam4FczpoFIQ7QdcakIBzB9I1qJrK2gZyUTdmJpulIFis_Is__2IlV2B3Vv7F1OXONgXzbAb6P7UR7oCbNQDOx8JAI6wyUCrQpgHVCl2ZHRW_ex-VhQ</recordid><startdate>20040206</startdate><enddate>20040206</enddate><creator>Baas, Annette F</creator><creator>Kuipers, Jeroen</creator><creator>van der Wel, Nicole N</creator><creator>Batlle, Eduard</creator><creator>Koerten, Henk K</creator><creator>Peters, Peter J</creator><creator>Clevers, Hans C</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</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>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20040206</creationdate><title>Complete Polarization of Single Intestinal Epithelial Cells upon Activation of LKB1 by STRAD</title><author>Baas, Annette F ; Kuipers, Jeroen ; van der Wel, Nicole N ; Batlle, Eduard ; Koerten, Henk K ; Peters, Peter J ; Clevers, Hans C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c557t-8befac6329df4ff9d290179b02de1c1ccac6e567d8fc498acb63dd3a17ad884b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Actin Cytoskeleton - metabolism</topic><topic>Actin Cytoskeleton - ultrastructure</topic><topic>Adaptor Proteins, Vesicular Transport - genetics</topic><topic>Adaptor Proteins, Vesicular Transport - metabolism</topic><topic>Caco-2 Cells</topic><topic>Cell Communication - genetics</topic><topic>Cell Polarity - physiology</topic><topic>Humans</topic><topic>Intercellular Junctions - genetics</topic><topic>Intestinal Mucosa - cytology</topic><topic>Intestinal Mucosa - metabolism</topic><topic>Intestinal Mucosa - ultrastructure</topic><topic>Membrane Proteins - metabolism</topic><topic>Microscopy, Electron</topic><topic>Microvilli - metabolism</topic><topic>Microvilli - ultrastructure</topic><topic>p120 GTPase Activating Protein - metabolism</topic><topic>Peutz-Jeghers Syndrome - genetics</topic><topic>Peutz-Jeghers Syndrome - metabolism</topic><topic>Phosphoproteins - metabolism</topic><topic>Protein-Serine-Threonine Kinases - genetics</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>Zonula Occludens-1 Protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Baas, Annette F</creatorcontrib><creatorcontrib>Kuipers, Jeroen</creatorcontrib><creatorcontrib>van der Wel, Nicole N</creatorcontrib><creatorcontrib>Batlle, Eduard</creatorcontrib><creatorcontrib>Koerten, Henk K</creatorcontrib><creatorcontrib>Peters, Peter J</creatorcontrib><creatorcontrib>Clevers, Hans C</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Baas, Annette F</au><au>Kuipers, Jeroen</au><au>van der Wel, Nicole N</au><au>Batlle, Eduard</au><au>Koerten, Henk K</au><au>Peters, Peter J</au><au>Clevers, Hans C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Complete Polarization of Single Intestinal Epithelial Cells upon Activation of LKB1 by STRAD</atitle><jtitle>Cell</jtitle><addtitle>Cell</addtitle><date>2004-02-06</date><risdate>2004</risdate><volume>116</volume><issue>3</issue><spage>457</spage><epage>466</epage><pages>457-466</pages><issn>0092-8674</issn><eissn>1097-4172</eissn><abstract>The
LKB1 gene encodes a serine/threonine kinase that is mutated in the Peutz-Jeghers cancer syndrome. LKB1 is homologous to the Par-4 polarity genes in
C. elegans and
D. melanogaster. We have previously reported the identification and characterization of an LKB1-specific adaptor protein, STRAD, which activates LKB1 and translocates it from nucleus to cytoplasm. We have now constructed intestinal epithelial cell lines in which inducible STRAD activates LKB1. Upon LKB1 activation, single cells rapidly remodel their actin cytoskeleton to form an apical brush border. The junctional proteins ZO-1 and p120 redistribute in a dotted circle peripheral to the brush border, in the absence of cell-cell contacts. Apical and basolateral markers sort to their respective membrane domains. We conclude that LKB1 can induce complete polarity in intestinal epithelial cells. In contrast to current thinking on polarization of simple epithelia, these cells can fully polarize in the absence of junctional cell-cell contacts.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>15016379</pmid><doi>10.1016/S0092-8674(04)00114-X</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Cell Press Free Archives; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; ScienceDirect Journals (5 years ago - present) |
| subjects | Actin Cytoskeleton - metabolism Actin Cytoskeleton - ultrastructure Adaptor Proteins, Vesicular Transport - genetics Adaptor Proteins, Vesicular Transport - metabolism Caco-2 Cells Cell Communication - genetics Cell Polarity - physiology Humans Intercellular Junctions - genetics Intestinal Mucosa - cytology Intestinal Mucosa - metabolism Intestinal Mucosa - ultrastructure Membrane Proteins - metabolism Microscopy, Electron Microvilli - metabolism Microvilli - ultrastructure p120 GTPase Activating Protein - metabolism Peutz-Jeghers Syndrome - genetics Peutz-Jeghers Syndrome - metabolism Phosphoproteins - metabolism Protein-Serine-Threonine Kinases - genetics Protein-Serine-Threonine Kinases - metabolism Zonula Occludens-1 Protein |
| title | Complete Polarization of Single Intestinal Epithelial Cells upon Activation of LKB1 by STRAD |
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