The Orphan Adhesion G Protein-coupled Receptor GPR97 Regulates Migration of Lymphatic Endothelial Cells via the Small GTPases RhoA and Cdc42*
Identifieur interne : 002E92 ( Pmc/Curation ); précédent : 002E91; suivant : 002E93The Orphan Adhesion G Protein-coupled Receptor GPR97 Regulates Migration of Lymphatic Endothelial Cells via the Small GTPases RhoA and Cdc42*
Auteurs : Nadejda Valtcheva [Suisse] ; Adriana Primorac [Suisse] ; Giorgia Jurisic [Suisse] ; Maija Hollmén [Suisse] ; Michael Detmar [Suisse]Source :
- The Journal of Biological Chemistry [ 0021-9258 ] ; 2013.
Abstract
Url:
DOI: 10.1074/jbc.M113.512954
PubMed: 24178298
PubMed Central: 3861625
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The Orphan Adhesion G Protein-coupled Receptor GPR97 Regulates Migration of Lymphatic Endothelial Cells via the Small GTPases RhoA and Cdc42<xref ref-type="fn" rid="FN1">*</xref></title><author><name sortKey="Valtcheva, Nadejda" sort="Valtcheva, Nadejda" uniqKey="Valtcheva N" first="Nadejda" last="Valtcheva">Nadejda Valtcheva</name><affiliation wicri:level="1"><nlm:aff id="aff1">From the Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>From the Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich</wicri:regionArea></affiliation></author><author><name sortKey="Primorac, Adriana" sort="Primorac, Adriana" uniqKey="Primorac A" first="Adriana" last="Primorac">Adriana Primorac</name><affiliation wicri:level="1"><nlm:aff id="aff1">From the Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>From the Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich</wicri:regionArea></affiliation></author><author><name sortKey="Jurisic, Giorgia" sort="Jurisic, Giorgia" uniqKey="Jurisic G" first="Giorgia" last="Jurisic">Giorgia Jurisic</name><affiliation wicri:level="1"><nlm:aff id="aff1">From the Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>From the Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich</wicri:regionArea></affiliation></author><author><name sortKey="Hollmen, Maija" sort="Hollmen, Maija" uniqKey="Hollmen M" first="Maija" last="Hollmén">Maija Hollmén</name><affiliation wicri:level="1"><nlm:aff id="aff1">From the Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>From the Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich</wicri:regionArea></affiliation></author><author><name sortKey="Detmar, Michael" sort="Detmar, Michael" uniqKey="Detmar M" first="Michael" last="Detmar">Michael Detmar</name><affiliation wicri:level="1"><nlm:aff id="aff1">From the Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>From the Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24178298</idno><idno type="pmc">3861625</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3861625</idno><idno type="RBID">PMC:3861625</idno><idno type="doi">10.1074/jbc.M113.512954</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">002E93</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002E93</idno><idno type="wicri:Area/Pmc/Curation">002E92</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">002E92</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The Orphan Adhesion G Protein-coupled Receptor GPR97 Regulates Migration of Lymphatic Endothelial Cells via the Small GTPases RhoA and Cdc42<xref ref-type="fn" rid="FN1">*</xref></title><author><name sortKey="Valtcheva, Nadejda" sort="Valtcheva, Nadejda" uniqKey="Valtcheva N" first="Nadejda" last="Valtcheva">Nadejda Valtcheva</name><affiliation wicri:level="1"><nlm:aff id="aff1">From the Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>From the Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich</wicri:regionArea></affiliation></author><author><name sortKey="Primorac, Adriana" sort="Primorac, Adriana" uniqKey="Primorac A" first="Adriana" last="Primorac">Adriana Primorac</name><affiliation wicri:level="1"><nlm:aff id="aff1">From the Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>From the Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich</wicri:regionArea></affiliation></author><author><name sortKey="Jurisic, Giorgia" sort="Jurisic, Giorgia" uniqKey="Jurisic G" first="Giorgia" last="Jurisic">Giorgia Jurisic</name><affiliation wicri:level="1"><nlm:aff id="aff1">From the Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>From the Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich</wicri:regionArea></affiliation></author><author><name sortKey="Hollmen, Maija" sort="Hollmen, Maija" uniqKey="Hollmen M" first="Maija" last="Hollmén">Maija Hollmén</name><affiliation wicri:level="1"><nlm:aff id="aff1">From the Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>From the Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich</wicri:regionArea></affiliation></author><author><name sortKey="Detmar, Michael" sort="Detmar, Michael" uniqKey="Detmar M" first="Michael" last="Detmar">Michael Detmar</name><affiliation wicri:level="1"><nlm:aff id="aff1">From the Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>From the Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich</wicri:regionArea></affiliation></author></analytic><series><title level="j">The Journal of Biological Chemistry</title><idno type="ISSN">0021-9258</idno><idno type="eISSN">1083-351X</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><bold>Background:</bold> The identification of G protein-coupled receptors (GPCRs) specific for the lymphatic endothelial cells (LECs) is essential for establishing drugs targeting the lymphatic system.</p><p><bold>Results:</bold> GPR97 is an orphan adhesion GPCR that regulates LEC migration.</p><p><bold>Conclusion:</bold> GPR97 is the first known adhesion GPCR involved in lymphatic remodeling.</p><p><bold>Significance:</bold> This first evidence that adhesion GPCRs govern LEC motility opens new possibilities for modulating lymphangiogenesis.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Biol Chem</journal-id><journal-id journal-id-type="iso-abbrev">J. Biol. Chem</journal-id><journal-id journal-id-type="hwp">jbc</journal-id><journal-id journal-id-type="pmc">jbc</journal-id><journal-id journal-id-type="publisher-id">JBC</journal-id><journal-title-group><journal-title>The Journal of Biological Chemistry</journal-title></journal-title-group><issn pub-type="ppub">0021-9258</issn><issn pub-type="epub">1083-351X</issn><publisher><publisher-name>American Society for Biochemistry and Molecular Biology</publisher-name><publisher-loc>9650 Rockville Pike, Bethesda, MD 20814, U.S.A.</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24178298</article-id><article-id pub-id-type="pmc">3861625</article-id><article-id pub-id-type="publisher-id">M113.512954</article-id><article-id pub-id-type="doi">10.1074/jbc.M113.512954</article-id><article-categories><subj-group subj-group-type="heading"><subject>Cell Biology</subject></subj-group></article-categories><title-group><article-title>The Orphan Adhesion G Protein-coupled Receptor GPR97 Regulates Migration of Lymphatic Endothelial Cells via the Small GTPases RhoA and Cdc42<xref ref-type="fn" rid="FN1">*</xref></article-title><alt-title alt-title-type="short">GPR97 Controls Lymphatic Endothelial Adhesion and Migration</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Valtcheva</surname><given-names>Nadejda</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Primorac</surname><given-names>Adriana</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Jurisic</surname><given-names>Giorgia</given-names></name><xref ref-type="aff" rid="aff1"></xref><xref ref-type="author-notes" rid="FN2"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hollmén</surname><given-names>Maija</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Detmar</surname><given-names>Michael</given-names></name><xref ref-type="aff" rid="aff1"></xref><xref ref-type="corresp" rid="cor1"><sup>2</sup></xref></contrib><aff id="aff1">From the Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland</aff></contrib-group><author-notes><corresp id="cor1"><label>2</label> To whom correspondence should be addressed: <addr-line>Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Wolfgang Pauli Str. 10, HCI H303, CH-8093 Zurich, Switzerland.</addr-line> Tel.: <phone>41-44-633-7361</phone>; Fax: <fax>41-44-633-1364</fax>; E-mail: <email>michael.detmar@pharma.ethz.ch</email>.</corresp><fn fn-type="present-address" id="FN2"><label>1</label><p>Present address: Novartis Institutes for BioMedical Research, Novartis Pharma AG, CH-4056 Basel, Switzerland.</p></fn></author-notes><pub-date pub-type="ppub"><day>13</day><month>12</month><year>2013</year></pub-date><pub-date pub-type="epub"><day>31</day><month>10</month><year>2013</year></pub-date><volume>288</volume><issue>50</issue><fpage>35736</fpage><lpage>35748</lpage><history><date date-type="received"><day>22</day><month>8</month><year>2013</year></date><date date-type="rev-recd"><day>21</day><month>10</month><year>2013</year></date></history><permissions><copyright-statement>© 2013 by The American Society for Biochemistry and Molecular Biology, Inc.</copyright-statement><copyright-year>2013</copyright-year></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zbc05013035736.pdf"></self-uri><abstract abstract-type="teaser"><p><bold>Background:</bold> The identification of G protein-coupled receptors (GPCRs) specific for the lymphatic endothelial cells (LECs) is essential for establishing drugs targeting the lymphatic system.</p><p><bold>Results:</bold> GPR97 is an orphan adhesion GPCR that regulates LEC migration.</p><p><bold>Conclusion:</bold> GPR97 is the first known adhesion GPCR involved in lymphatic remodeling.</p><p><bold>Significance:</bold> This first evidence that adhesion GPCRs govern LEC motility opens new possibilities for modulating lymphangiogenesis.</p></abstract><abstract><p>The important role of the lymphatic vascular system in pathological conditions such as inflammation and cancer has been increasingly recognized, but its potential as a pharmacological target is poorly exploited. Our study aimed at the identification and molecular characterization of lymphatic-specific G protein-coupled receptors (GPCRs) to assess new targets for pharmacological manipulation of the lymphatic vascular system. We used a TaqMan quantitative RT-PCR-based low density array to determine the GPCR expression profiles of <italic>ex vivo</italic> isolated intestinal mouse lymphatic (LECs) and blood vascular endothelial cells (BECs). GPR97, an orphan adhesion GPCR of unknown function, was the most highly and specifically expressed GPCR in mouse lymphatic endothelium. Using siRNA silencing, we found that GPR97-deficient primary human LECs displayed increased adhesion and collective cell migration, whereas single cell migration was decreased as compared with nontargeting siRNA-transfected control LECs. Loss of GPR97 shifted the ratio of active Cdc42 and RhoA and initiated cytoskeletal rearrangements, including F-actin redistribution, paxillin and PAK4 phosphorylation, and β1-integrin activation. Our data suggest a possible role of GPR97 in lymphatic remodeling and furthermore provide the first insights into the biological functions of GPR97.</p></abstract><kwd-group><kwd>7-Helix Receptor</kwd><kwd>Adhesion</kwd><kwd>Cytoskeleton</kwd><kwd>Endothelial Cell</kwd><kwd>Integrin</kwd><kwd>Lymphangiogenesis</kwd><kwd>Pb99</kwd><kwd>Wound Healing Assay</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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