Links to Exploration step
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">LRRK2 localizes to endosomes and interacts with clathrin-light chains to limit Rac1 activation</title><author><name sortKey="Schreij, Andrea Ma" sort="Schreij, Andrea Ma" uniqKey="Schreij A" first="Andrea Ma" last="Schreij">Andrea Ma Schreij</name><affiliation><nlm:aff id="au1"></nlm:aff></affiliation></author><author><name sortKey="Chaineau, Mathilde" sort="Chaineau, Mathilde" uniqKey="Chaineau M" first="Mathilde" last="Chaineau">Mathilde Chaineau</name><affiliation><nlm:aff id="au1"></nlm:aff></affiliation></author><author><name sortKey="Ruan, Wenjing" sort="Ruan, Wenjing" uniqKey="Ruan W" first="Wenjing" last="Ruan">Wenjing Ruan</name><affiliation><nlm:aff id="au1"></nlm:aff></affiliation></author><author><name sortKey="Lin, Susan" sort="Lin, Susan" uniqKey="Lin S" first="Susan" last="Lin">Susan Lin</name><affiliation><nlm:aff id="au1"></nlm:aff></affiliation></author><author><name sortKey="Barker, Philip A" sort="Barker, Philip A" uniqKey="Barker P" first="Philip A" last="Barker">Philip A. Barker</name><affiliation><nlm:aff id="au1"></nlm:aff></affiliation></author><author><name sortKey="Fon, Edward A" sort="Fon, Edward A" uniqKey="Fon E" first="Edward A" last="Fon">Edward A. Fon</name><affiliation><nlm:aff id="au1"></nlm:aff></affiliation></author><author><name sortKey="Mcpherson, Peter S" sort="Mcpherson, Peter S" uniqKey="Mcpherson P" first="Peter S" last="Mcpherson">Peter S. Mcpherson</name><affiliation><nlm:aff id="au1"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25427558</idno><idno type="pmc">4304731</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4304731</idno><idno type="RBID">PMC:4304731</idno><idno type="doi">10.15252/embr.201438714</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000533</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000533</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">LRRK2 localizes to endosomes and interacts with clathrin-light chains to limit Rac1 activation</title><author><name sortKey="Schreij, Andrea Ma" sort="Schreij, Andrea Ma" uniqKey="Schreij A" first="Andrea Ma" last="Schreij">Andrea Ma Schreij</name><affiliation><nlm:aff id="au1"></nlm:aff></affiliation></author><author><name sortKey="Chaineau, Mathilde" sort="Chaineau, Mathilde" uniqKey="Chaineau M" first="Mathilde" last="Chaineau">Mathilde Chaineau</name><affiliation><nlm:aff id="au1"></nlm:aff></affiliation></author><author><name sortKey="Ruan, Wenjing" sort="Ruan, Wenjing" uniqKey="Ruan W" first="Wenjing" last="Ruan">Wenjing Ruan</name><affiliation><nlm:aff id="au1"></nlm:aff></affiliation></author><author><name sortKey="Lin, Susan" sort="Lin, Susan" uniqKey="Lin S" first="Susan" last="Lin">Susan Lin</name><affiliation><nlm:aff id="au1"></nlm:aff></affiliation></author><author><name sortKey="Barker, Philip A" sort="Barker, Philip A" uniqKey="Barker P" first="Philip A" last="Barker">Philip A. Barker</name><affiliation><nlm:aff id="au1"></nlm:aff></affiliation></author><author><name sortKey="Fon, Edward A" sort="Fon, Edward A" uniqKey="Fon E" first="Edward A" last="Fon">Edward A. Fon</name><affiliation><nlm:aff id="au1"></nlm:aff></affiliation></author><author><name sortKey="Mcpherson, Peter S" sort="Mcpherson, Peter S" uniqKey="Mcpherson P" first="Peter S" last="Mcpherson">Peter S. Mcpherson</name><affiliation><nlm:aff id="au1"></nlm:aff></affiliation></author></analytic><series><title level="j">EMBO Reports</title><idno type="ISSN">1469-221X</idno><idno type="eISSN">1469-3178</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of dominant-inherited Parkinson's disease (PD), and yet we do not fully understand the physiological function(s) of LRRK2. Various components of the clathrin machinery have been recently found mutated in familial forms of PD. Here, we provide molecular insight into the association of LRRK2 with the clathrin machinery. We report that through its GTPase domain, LRRK2 binds directly to clathrin-light chains (CLCs). Using genome-edited HA-LRRK2 cells, we localize LRRK2 to endosomes on the degradative pathway, where it partially co-localizes with CLCs. Knockdown of CLCs and/or LRRK2 enhances the activation of the small GTPase Rac1, leading to alterations in cell morphology, including the disruption of neuronal dendritic spines. In <italic>Drosphila</italic>, a minimal rough eye phenotype caused by overexpression of Rac1, is dramatically enhanced by loss of function of CLC and LRRK2 homologues, confirming the importance of this pathway <italic>in vivo</italic>. Our data identify a new pathway in which CLCs function with LRRK2 to control Rac1 activation on endosomes, providing a new link between the clathrin machinery, the cytoskeleton and PD.</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">EMBO Rep</journal-id><journal-id journal-id-type="iso-abbrev">EMBO Rep</journal-id><journal-id journal-id-type="publisher-id">embr</journal-id><journal-title-group><journal-title>EMBO Reports</journal-title></journal-title-group><issn pub-type="ppub">1469-221X</issn><issn pub-type="epub">1469-3178</issn><publisher><publisher-name>BlackWell Publishing Ltd</publisher-name><publisher-loc>Oxford, UK</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25427558</article-id><article-id pub-id-type="pmc">4304731</article-id><article-id pub-id-type="doi">10.15252/embr.201438714</article-id><article-categories><subj-group subj-group-type="heading"><subject>Scientific Reports</subject></subj-group></article-categories><title-group><article-title>LRRK2 localizes to endosomes and interacts with clathrin-light chains to limit Rac1 activation</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Schreij</surname><given-names>Andrea MA</given-names></name><xref ref-type="aff" rid="au1"></xref></contrib><contrib contrib-type="author"><name><surname>Chaineau</surname><given-names>Mathilde</given-names></name><xref ref-type="aff" rid="au1"></xref></contrib><contrib contrib-type="author"><name><surname>Ruan</surname><given-names>Wenjing</given-names></name><xref ref-type="aff" rid="au1"></xref></contrib><contrib contrib-type="author"><name><surname>Lin</surname><given-names>Susan</given-names></name><xref ref-type="aff" rid="au1"></xref></contrib><contrib contrib-type="author"><name><surname>Barker</surname><given-names>Philip A</given-names></name><xref ref-type="aff" rid="au1"></xref></contrib><contrib contrib-type="author"><name><surname>Fon</surname><given-names>Edward A</given-names></name><xref ref-type="aff" rid="au1"></xref><xref ref-type="corresp" rid="cor1">*</xref></contrib><contrib contrib-type="author"><name><surname>McPherson</surname><given-names>Peter S</given-names></name><xref ref-type="aff" rid="au1"></xref><xref ref-type="corresp" rid="cor2">**</xref></contrib><aff id="au1"><institution>Department of Neurology and Neurosurgery and McGill Parkinson Program, Montreal Neurological Institute, McGill University</institution><addr-line>Montreal, Quebec, Canada</addr-line></aff></contrib-group><author-notes><corresp id="cor1">*Corresponding author. Tel: +1 514 398-8398; E-mail: <email>ted.fon@mcgill.ca</email></corresp><corresp id="cor2">**Corresponding author. Tel: +1 514 398 7355; E-mail: <email>peter.mcpherson@mcgill.ca</email></corresp><fn><p><bold>Subject Categories</bold> Membrane & Intracellular Transport; Molecular Biology of Disease; Neuroscience</p></fn></author-notes><pub-date pub-type="ppub"><month>1</month><year>2015</year></pub-date><pub-date pub-type="epub"><day>26</day><month>11</month><year>2014</year></pub-date><volume>16</volume><issue>1</issue><fpage>79</fpage><lpage>86</lpage><history><date date-type="received"><day>06</day><month>3</month><year>2014</year></date><date date-type="rev-recd"><day>14</day><month>10</month><year>2014</year></date><date date-type="accepted"><day>17</day><month>10</month><year>2014</year></date></history><permissions><copyright-statement>© 2014 The Authors</copyright-statement><copyright-year>2014</copyright-year></permissions><abstract><p>Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of dominant-inherited Parkinson's disease (PD), and yet we do not fully understand the physiological function(s) of LRRK2. Various components of the clathrin machinery have been recently found mutated in familial forms of PD. Here, we provide molecular insight into the association of LRRK2 with the clathrin machinery. We report that through its GTPase domain, LRRK2 binds directly to clathrin-light chains (CLCs). Using genome-edited HA-LRRK2 cells, we localize LRRK2 to endosomes on the degradative pathway, where it partially co-localizes with CLCs. Knockdown of CLCs and/or LRRK2 enhances the activation of the small GTPase Rac1, leading to alterations in cell morphology, including the disruption of neuronal dendritic spines. In <italic>Drosphila</italic>, a minimal rough eye phenotype caused by overexpression of Rac1, is dramatically enhanced by loss of function of CLC and LRRK2 homologues, confirming the importance of this pathway <italic>in vivo</italic>. Our data identify a new pathway in which CLCs function with LRRK2 to control Rac1 activation on endosomes, providing a new link between the clathrin machinery, the cytoskeleton and PD.</p></abstract><kwd-group><kwd>clathrin</kwd><kwd><italic>Drosophila melanogaster</italic></kwd><kwd>endosomes</kwd><kwd>Parkinson's disease</kwd><kwd>Rac1</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Canada/explor/ParkinsonCanadaV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000533 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 000533 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Canada
|area= ParkinsonCanadaV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé=
|texte=
}}
| This area was generated with Dilib version V0.6.29. |  |