p120RasGAP Protein Mediates Netrin-1 Protein-induced Cortical Axon Outgrowth and Guidance*
Identifieur interne : 001E19 ( Ncbi/Curation ); précédent : 001E18; suivant : 001E20p120RasGAP 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
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: Pour aller vers cette notice dans l'étape Curation :000123
- to stream Pmc, to step Curation: Pour aller vers cette notice dans l'étape Curation :000123
- to stream Pmc, to step Checkpoint: Pour aller vers cette notice dans l'étape Curation :000175
- to stream Ncbi, to step Merge: Pour aller vers cette notice dans l'étape Curation :001E19
Links to Exploration step
PMC:4813483Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">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>
</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>
<idno type="wicri:Area/Pmc/Curation">000123</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000123</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000175</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000175</idno>
<idno type="wicri:Area/Ncbi/Merge">001E19</idno>
<idno type="wicri:Area/Ncbi/Curation">001E19</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>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Canada/explor/ParkinsonCanadaV1/Data/Ncbi/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001E19 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Ncbi/Curation/biblio.hfd -nk 001E19 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Canada |area= ParkinsonCanadaV1 |flux= Ncbi |étape= Curation |type= RBID |clé= PMC:4813483 |texte= p120RasGAP Protein Mediates Netrin-1 Protein-induced Cortical Axon Outgrowth and Guidance* }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Ncbi/Curation/RBID.i -Sk "pubmed:26710849" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Ncbi/Curation/biblio.hfd \ | NlmPubMed2Wicri -a ParkinsonCanadaV1
![]() | This area was generated with Dilib version V0.6.29. | ![]() |