p120RasGAP Protein Mediates Netrin-1 Protein-induced Cortical Axon Outgrowth and Guidance*
Identifieur interne : 000123 ( Pmc/Corpus ); précédent : 000122; suivant : 000124p120RasGAP Protein Mediates Netrin-1 Protein-induced Cortical Axon Outgrowth and Guidance*
Auteurs : Judith Antoine-Bertrand ; Philippe M. Duquette ; Ricardo Alchini ; Timothy E. Kennedy ; Alyson E. Fournier ; Nathalie Lamarche-VaneSource :
- The Journal of Biological Chemistry [ 0021-9258 ] ; 2015.
Abstract
The receptor deleted in colorectal cancer (DCC) mediates the attraction of growing axons to netrin-1 during brain development. In response to netrin-1 stimulation, DCC becomes a signaling platform to recruit proteins that promote axon outgrowth and guidance. The Ras GTPase-activating protein (GAP) p120RasGAP inhibits Ras activity and mediates neurite retraction and growth cone collapse in response to repulsive guidance cues. Here we show an interaction between p120RasGAP and DCC that positively regulates netrin-1-mediated axon outgrowth and guidance in embryonic cortical neurons. In response to netrin-1, p120RasGAP is recruited to DCC in growth cones and forms a multiprotein complex with focal adhesion kinase and ERK. We found that Ras/ERK activities are elevated aberrantly in p120RasGAP-deficient neurons. Moreover, the expression of p120RasGAP Src homology 2 (SH2)-SH3-SH2 domains, which interact with the C-terminal tail of DCC, is sufficient to restore netrin-1-dependent axon outgrowth in p120RasGAP-deficient neurons. We provide a novel mechanism that exploits the scaffolding properties of the N terminus of p120RasGAP to tightly regulate netrin-1/DCC-dependent axon outgrowth and guidance.
Url:
DOI: 10.1074/jbc.M115.674846
PubMed: 26710849
PubMed Central: 4813483
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PMC:4813483Le document en format XML
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Duquette</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Alchini, Ricardo" sort="Alchini, Ricardo" uniqKey="Alchini R" first="Ricardo" last="Alchini">Ricardo Alchini</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Kennedy, Timothy E" sort="Kennedy, Timothy E" uniqKey="Kennedy T" first="Timothy E." last="Kennedy">Timothy E. Kennedy</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Fournier, Alyson E" sort="Fournier, Alyson E" uniqKey="Fournier A" first="Alyson E." last="Fournier">Alyson E. Fournier</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Lamarche Vane, Nathalie" sort="Lamarche Vane, Nathalie" uniqKey="Lamarche Vane N" first="Nathalie" last="Lamarche-Vane">Nathalie Lamarche-Vane</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26710849</idno><idno type="pmc">4813483</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4813483</idno><idno type="RBID">PMC:4813483</idno><idno type="doi">10.1074/jbc.M115.674846</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000123</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000123</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">p120RasGAP Protein Mediates Netrin-1 Protein-induced Cortical Axon Outgrowth and Guidance<xref ref-type="fn" rid="FN1">*</xref><xref ref-type="fn" rid="FN2"><sup><inline-graphic xlink:href="sbox.jpg"></inline-graphic></sup></xref></title><author><name sortKey="Antoine Bertrand, Judith" sort="Antoine Bertrand, Judith" uniqKey="Antoine Bertrand J" first="Judith" last="Antoine-Bertrand">Judith Antoine-Bertrand</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Duquette, Philippe M" sort="Duquette, Philippe M" uniqKey="Duquette P" first="Philippe M." last="Duquette">Philippe M. Duquette</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Alchini, Ricardo" sort="Alchini, Ricardo" uniqKey="Alchini R" first="Ricardo" last="Alchini">Ricardo Alchini</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Kennedy, Timothy E" sort="Kennedy, Timothy E" uniqKey="Kennedy T" first="Timothy E." last="Kennedy">Timothy E. Kennedy</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Fournier, Alyson E" sort="Fournier, Alyson E" uniqKey="Fournier A" first="Alyson E." last="Fournier">Alyson E. Fournier</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Lamarche Vane, Nathalie" sort="Lamarche Vane, Nathalie" uniqKey="Lamarche Vane N" first="Nathalie" last="Lamarche-Vane">Nathalie Lamarche-Vane</name><affiliation><nlm:aff id="aff1"></nlm:aff></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="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The receptor deleted in colorectal cancer (DCC) mediates the attraction of growing axons to netrin-1 during brain development. In response to netrin-1 stimulation, DCC becomes a signaling platform to recruit proteins that promote axon outgrowth and guidance. The Ras GTPase-activating protein (GAP) p120RasGAP inhibits Ras activity and mediates neurite retraction and growth cone collapse in response to repulsive guidance cues. Here we show an interaction between p120RasGAP and DCC that positively regulates netrin-1-mediated axon outgrowth and guidance in embryonic cortical neurons. In response to netrin-1, p120RasGAP is recruited to DCC in growth cones and forms a multiprotein complex with focal adhesion kinase and ERK. We found that Ras/ERK activities are elevated aberrantly in p120RasGAP-deficient neurons. Moreover, the expression of p120RasGAP Src homology 2 (SH2)-SH3-SH2 domains, which interact with the C-terminal tail of DCC, is sufficient to restore netrin-1-dependent axon outgrowth in p120RasGAP-deficient neurons. We provide a novel mechanism that exploits the scaffolding properties of the N terminus of p120RasGAP to tightly regulate netrin-1/DCC-dependent axon outgrowth and guidance.</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>11200 Rockville Pike, Suite 302, Rockville, MD 20852-3110, U.S.A.</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26710849</article-id><article-id pub-id-type="pmc">4813483</article-id><article-id pub-id-type="publisher-id">M115.674846</article-id><article-id pub-id-type="doi">10.1074/jbc.M115.674846</article-id><article-categories><subj-group subj-group-type="heading"><subject>Neurobiology</subject></subj-group></article-categories><title-group><article-title>p120RasGAP Protein Mediates Netrin-1 Protein-induced Cortical Axon Outgrowth and Guidance<xref ref-type="fn" rid="FN1">*</xref><xref ref-type="fn" rid="FN2"><sup><inline-graphic xlink:href="sbox.jpg"></inline-graphic></sup></xref></article-title><alt-title alt-title-type="short">p120RasGAP Regulates Axon Outgrowth and Guidance</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Antoine-Bertrand</surname><given-names>Judith</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Duquette</surname><given-names>Philippe M.</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="author-notes" rid="FN3"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Alchini</surname><given-names>Ricardo</given-names></name><xref ref-type="aff" rid="aff2"><sup>§</sup></xref><xref ref-type="author-notes" rid="FN4"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kennedy</surname><given-names>Timothy E.</given-names></name><xref ref-type="aff" rid="aff2"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Fournier</surname><given-names>Alyson E.</given-names></name><xref ref-type="aff" rid="aff2"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lamarche-Vane</surname><given-names>Nathalie</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="corresp" rid="cor1"><sup>3</sup></xref></contrib><aff id="aff1">From the<label>‡</label>Department of Anatomy and Cell Biology and Cancer Research Program, Research Institute of McGill University Health Centre, McGill University, Montreal, Quebec, H4A 3J1 Canada and</aff><aff id="aff2">the<label>§</label>Department of Neurology and Neurosurgery, Montreal Neurological Institute, Montreal, Quebec, H3A 2B4 Canada</aff></contrib-group><author-notes><corresp id="cor1"><label>3</label> Recipient of a Fonds de la Recherche en Santé du Québec Chercheur-National and a William Dawson scholar. To whom correspondence should be addressed: <addr-line>Centre for Translational Biology, RI-MUHC, 1001 Boul. Décarie, Rm. E02.6230, Montreal, Quebec H4A 3J1, Canada.</addr-line> Tel.: <phone>514-934-1934, ext. 76166</phone>; E-mail: <email>nathalie.lamarche@mcgill.ca</email>.</corresp><fn fn-type="other" id="FN3"><label>1</label><p>Recipient of a Fonds de la Recherche en Santé du Québec doctoral studentship.</p></fn><fn fn-type="other" id="FN4"><label>2</label><p>Recipient of a Canadian Institute of Health Research Vanier studentship and a Lloyd Carr-Harris fellowship from McGill University.</p></fn></author-notes><pub-date pub-type="ppub"><day>26</day><month>2</month><year>2016</year></pub-date><pub-date pub-type="epub"><day>28</day><month>12</month><year>2015</year></pub-date><volume>291</volume><issue>9</issue><fpage>4589</fpage><lpage>4602</lpage><history><date date-type="received"><day>25</day><month>6</month><year>2015</year></date><date date-type="rev-recd"><day>24</day><month>12</month><year>2015</year></date></history><permissions><copyright-statement>© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.</copyright-statement><copyright-year>2016</copyright-year><copyright-holder>The American Society for Biochemistry and Molecular Biology, Inc.</copyright-holder></permissions><self-uri content-type="pdf" xlink:href="zbc00916004589.pdf"></self-uri><abstract><p>The receptor deleted in colorectal cancer (DCC) mediates the attraction of growing axons to netrin-1 during brain development. In response to netrin-1 stimulation, DCC becomes a signaling platform to recruit proteins that promote axon outgrowth and guidance. The Ras GTPase-activating protein (GAP) p120RasGAP inhibits Ras activity and mediates neurite retraction and growth cone collapse in response to repulsive guidance cues. Here we show an interaction between p120RasGAP and DCC that positively regulates netrin-1-mediated axon outgrowth and guidance in embryonic cortical neurons. In response to netrin-1, p120RasGAP is recruited to DCC in growth cones and forms a multiprotein complex with focal adhesion kinase and ERK. We found that Ras/ERK activities are elevated aberrantly in p120RasGAP-deficient neurons. Moreover, the expression of p120RasGAP Src homology 2 (SH2)-SH3-SH2 domains, which interact with the C-terminal tail of DCC, is sufficient to restore netrin-1-dependent axon outgrowth in p120RasGAP-deficient neurons. We provide a novel mechanism that exploits the scaffolding properties of the N terminus of p120RasGAP to tightly regulate netrin-1/DCC-dependent axon outgrowth and guidance.</p></abstract><kwd-group><kwd>neurite outgrowth</kwd><kwd>neurobiology</kwd><kwd>neurodevelopment</kwd><kwd>Ras protein</kwd><kwd>signal transduction</kwd><kwd>DCC</kwd><kwd>netrin-1</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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