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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Parkin-mediated Monoubiquitination of the PDZ Protein PICK1 Regulates the Activity of Acid-sensing Ion Channels</title><author><name sortKey="Joch, Monica" sort="Joch, Monica" uniqKey="Joch M" first="Monica" last="Joch">Monica Joch</name><affiliation><nlm:aff id="aff1">*Centre for Neuronal Survival and</nlm:aff></affiliation></author><author><name sortKey="Ase, Ariel R" sort="Ase, Ariel R" uniqKey="Ase A" first="Ariel R." last="Ase">Ariel R. Ase</name><affiliation><nlm:aff wicri:cut="; and" id="aff2">Cell Biology of Excitable Tissues, Montreal Neurological Institute, McGill University, Montreal, Quebec, H3A 2B4, Canada</nlm:aff></affiliation></author><author><name sortKey="Chen, Carol X Q" sort="Chen, Carol X Q" uniqKey="Chen C" first="Carol X.-Q." last="Chen">Carol X.-Q. Chen</name><affiliation><nlm:aff id="aff1">*Centre for Neuronal Survival and</nlm:aff></affiliation></author><author><name sortKey="Macdonald, Penny A" sort="Macdonald, Penny A" uniqKey="Macdonald P" first="Penny A." last="Macdonald">Penny A. Macdonald</name><affiliation><nlm:aff id="aff1">*Centre for Neuronal Survival and</nlm:aff></affiliation></author><author><name sortKey="Kontogiannea, Maria" sort="Kontogiannea, Maria" uniqKey="Kontogiannea M" first="Maria" last="Kontogiannea">Maria Kontogiannea</name><affiliation><nlm:aff id="aff1">*Centre for Neuronal Survival and</nlm:aff></affiliation></author><author><name sortKey="Corera, Amadou T" sort="Corera, Amadou T" uniqKey="Corera A" first="Amadou T." last="Corera">Amadou T. Corera</name><affiliation><nlm:aff id="aff1">*Centre for Neuronal Survival and</nlm:aff></affiliation></author><author><name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name><affiliation><nlm:aff id="aff3">Institut National de la Santé et de la Recherche Médicale U 679, Groupe Hospitalier Pitié-Salpêtrière, 75651 Paris Cedex 13, France</nlm:aff></affiliation></author><author><name sortKey="Seguela, Philippe" sort="Seguela, Philippe" uniqKey="Seguela P" first="Philippe" last="Séguéla">Philippe Séguéla</name><affiliation><nlm:aff wicri:cut="; and" id="aff2">Cell Biology of Excitable Tissues, Montreal Neurological Institute, McGill University, Montreal, Quebec, H3A 2B4, Canada</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="aff1">*Centre for Neuronal Survival and</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">17553932</idno><idno type="pmc">1949385</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1949385</idno><idno type="RBID">PMC:1949385</idno><idno type="doi">10.1091/mbc.E05-11-1027</idno><date when="2007">2007</date><idno type="wicri:Area/Pmc/Corpus">000603</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000603</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Parkin-mediated Monoubiquitination of the PDZ Protein PICK1 Regulates the Activity of Acid-sensing Ion Channels</title><author><name sortKey="Joch, Monica" sort="Joch, Monica" uniqKey="Joch M" first="Monica" last="Joch">Monica Joch</name><affiliation><nlm:aff id="aff1">*Centre for Neuronal Survival and</nlm:aff></affiliation></author><author><name sortKey="Ase, Ariel R" sort="Ase, Ariel R" uniqKey="Ase A" first="Ariel R." last="Ase">Ariel R. Ase</name><affiliation><nlm:aff wicri:cut="; and" id="aff2">Cell Biology of Excitable Tissues, Montreal Neurological Institute, McGill University, Montreal, Quebec, H3A 2B4, Canada</nlm:aff></affiliation></author><author><name sortKey="Chen, Carol X Q" sort="Chen, Carol X Q" uniqKey="Chen C" first="Carol X.-Q." last="Chen">Carol X.-Q. Chen</name><affiliation><nlm:aff id="aff1">*Centre for Neuronal Survival and</nlm:aff></affiliation></author><author><name sortKey="Macdonald, Penny A" sort="Macdonald, Penny A" uniqKey="Macdonald P" first="Penny A." last="Macdonald">Penny A. Macdonald</name><affiliation><nlm:aff id="aff1">*Centre for Neuronal Survival and</nlm:aff></affiliation></author><author><name sortKey="Kontogiannea, Maria" sort="Kontogiannea, Maria" uniqKey="Kontogiannea M" first="Maria" last="Kontogiannea">Maria Kontogiannea</name><affiliation><nlm:aff id="aff1">*Centre for Neuronal Survival and</nlm:aff></affiliation></author><author><name sortKey="Corera, Amadou T" sort="Corera, Amadou T" uniqKey="Corera A" first="Amadou T." last="Corera">Amadou T. Corera</name><affiliation><nlm:aff id="aff1">*Centre for Neuronal Survival and</nlm:aff></affiliation></author><author><name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name><affiliation><nlm:aff id="aff3">Institut National de la Santé et de la Recherche Médicale U 679, Groupe Hospitalier Pitié-Salpêtrière, 75651 Paris Cedex 13, France</nlm:aff></affiliation></author><author><name sortKey="Seguela, Philippe" sort="Seguela, Philippe" uniqKey="Seguela P" first="Philippe" last="Séguéla">Philippe Séguéla</name><affiliation><nlm:aff wicri:cut="; and" id="aff2">Cell Biology of Excitable Tissues, Montreal Neurological Institute, McGill University, Montreal, Quebec, H3A 2B4, Canada</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="aff1">*Centre for Neuronal Survival and</nlm:aff></affiliation></author></analytic><series><title level="j">Molecular Biology of the Cell</title><idno type="ISSN">1059-1524</idno><idno type="eISSN">1939-4586</idno><imprint><date when="2007">2007</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Mutations in the <italic>parkin</italic> gene result in an autosomal recessive juvenile-onset form of Parkinson's disease. As an E3 ubiquitin-ligase, parkin promotes the attachment of ubiquitin onto specific substrate proteins. Defects in the ubiquitination of parkin substrates are therefore believed to lead to neurodegeneration in Parkinson's disease. Here, we identify the PSD-95/Discs-large/Zona Occludens-1 (PDZ) protein PICK1 as a novel parkin substrate. We find that parkin binds PICK1 via a PDZ-mediated interaction, which predominantly promotes PICK1 monoubiquitination rather than polyubiquitination. Consistent with monoubiquitination and recent work implicating parkin in proteasome-independent pathways, parkin does not promote PICK1 degradation. However, parkin regulates the effects of PICK1 on one of its other PDZ partners, the acid-sensing ion channel (ASIC). Overexpression of wild-type, but not PDZ binding– or E3 ubiquitin-ligase–defective parkin abolishes the previously described, protein kinase C-induced, PICK1-dependent potentiation of ASIC2a currents in non-neuronal cells. Conversely, the loss of parkin in hippocampal neurons from parkin knockout mice unmasks prominent potentiation of native ASIC currents, which is normally suppressed by endogenous parkin in wild-type neurons. Given that ASIC channels contribute to excitotoxicity, our work provides a mechanism explaining how defects in parkin-mediated PICK1 monoubiquitination could enhance ASIC activity and thereby promote neurodegeneration in Parkinson's disease.</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">Mol Biol Cell</journal-id><journal-id journal-id-type="publisher-id">Mol. Bio. Cell</journal-id><journal-title>Molecular Biology of the Cell</journal-title><issn pub-type="ppub">1059-1524</issn><issn pub-type="epub">1939-4586</issn><publisher><publisher-name>The American Society for Cell Biology</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">17553932</article-id><article-id pub-id-type="pmc">1949385</article-id><article-id pub-id-type="publisher-id">3239259</article-id><article-id pub-id-type="doi">10.1091/mbc.E05-11-1027</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group></article-categories><title-group><article-title>Parkin-mediated Monoubiquitination of the PDZ Protein PICK1 Regulates the Activity of Acid-sensing Ion Channels</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Joch</surname><given-names>Monica</given-names></name><xref ref-type="aff" rid="aff1">*</xref><xref ref-type="author-notes" rid="FN1"><sup>†</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ase</surname><given-names>Ariel R.</given-names></name><xref ref-type="author-notes" rid="FN1"><sup>†</sup></xref><xref ref-type="aff" rid="aff2"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Carol X.-Q.</given-names></name><xref ref-type="aff" rid="aff1">*</xref><xref ref-type="author-notes" rid="FN1"><sup>†</sup></xref></contrib><contrib contrib-type="author"><name><surname>MacDonald</surname><given-names>Penny A.</given-names></name><xref ref-type="aff" rid="aff1">*</xref></contrib><contrib contrib-type="author"><name><surname>Kontogiannea</surname><given-names>Maria</given-names></name><xref ref-type="aff" rid="aff1">*</xref></contrib><contrib contrib-type="author"><name><surname>Corera</surname><given-names>Amadou T.</given-names></name><xref ref-type="aff" rid="aff1">*</xref></contrib><contrib contrib-type="author"><name><surname>Brice</surname><given-names>Alexis</given-names></name><xref ref-type="aff" rid="aff3"><sup>§</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Séguéla</surname><given-names>Philippe</given-names></name><xref ref-type="aff" rid="aff2"><sup>‡</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Fon</surname><given-names>Edward A.</given-names></name><xref ref-type="aff" rid="aff1">*</xref></contrib><aff id="aff1">*Centre for Neuronal Survival and</aff><aff id="aff2"><sup>‡</sup>Cell Biology of Excitable Tissues, Montreal Neurological Institute, McGill University, Montreal, Quebec, H3A 2B4, Canada; and</aff><aff id="aff3"><sup>§</sup>Institut National de la Santé et de la Recherche Médicale U 679, Groupe Hospitalier Pitié-Salpêtrière, 75651 Paris Cedex 13, France</aff></contrib-group><contrib-group><contrib contrib-type="editor"><name><surname>Margolis</surname><given-names>Ben</given-names></name><role>Monitoring Editor</role></contrib></contrib-group><author-notes><corresp>Address correspondence to: Edward A. Fon (<email>ted.fon@mcgill.ca</email>) or Philippe Séguéla (<email>philippe.seguela@mcgill.ca</email>).</corresp><fn fn-type="equal" id="FN1"><p><sup>†</sup> These authors contributed equally to this work.</p></fn></author-notes><pub-date pub-type="ppub"><month>8</month><year>2007</year></pub-date><volume>18</volume><issue>8</issue><fpage>3105</fpage><lpage>3118</lpage><history><date date-type="received"><day>8</day><month>11</month><year>2005</year></date><date date-type="rev-recd"><day>22</day><month>5</month><year>2007</year></date><date date-type="accepted"><day>25</day><month>5</month><year>2007</year></date></history><copyright-statement>© 2007 by The American Society for Cell Biology</copyright-statement><copyright-year>2007</copyright-year><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zmk00807003105.pdf"></self-uri><self-uri xlink:title="pdf" xlink:href="zmk00807003105.pdf"></self-uri><abstract><p>Mutations in the <italic>parkin</italic> gene result in an autosomal recessive juvenile-onset form of Parkinson's disease. As an E3 ubiquitin-ligase, parkin promotes the attachment of ubiquitin onto specific substrate proteins. Defects in the ubiquitination of parkin substrates are therefore believed to lead to neurodegeneration in Parkinson's disease. Here, we identify the PSD-95/Discs-large/Zona Occludens-1 (PDZ) protein PICK1 as a novel parkin substrate. We find that parkin binds PICK1 via a PDZ-mediated interaction, which predominantly promotes PICK1 monoubiquitination rather than polyubiquitination. Consistent with monoubiquitination and recent work implicating parkin in proteasome-independent pathways, parkin does not promote PICK1 degradation. However, parkin regulates the effects of PICK1 on one of its other PDZ partners, the acid-sensing ion channel (ASIC). Overexpression of wild-type, but not PDZ binding– or E3 ubiquitin-ligase–defective parkin abolishes the previously described, protein kinase C-induced, PICK1-dependent potentiation of ASIC2a currents in non-neuronal cells. Conversely, the loss of parkin in hippocampal neurons from parkin knockout mice unmasks prominent potentiation of native ASIC currents, which is normally suppressed by endogenous parkin in wild-type neurons. Given that ASIC channels contribute to excitotoxicity, our work provides a mechanism explaining how defects in parkin-mediated PICK1 monoubiquitination could enhance ASIC activity and thereby promote neurodegeneration in Parkinson's disease.</p></abstract><custom-meta-wrap><custom-meta><meta-name>PDF</meta-name><meta-value><uri xlink:type="simple" xlink:href="zmk00807003105.pdf"></uri></meta-value></custom-meta></custom-meta-wrap></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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