PSD-95 expression controls l-DOPA dyskinesia through dopamine D1 receptor trafficking
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Auteurs : Gregory Porras [France] ; Amandine Berthet [France] ; Benjamin Dehay [France] ; Qin Li [République populaire de Chine] ; Laurent Ladepeche [France] ; Elisabeth Normand [France] ; Sandra Dovero [France] ; Audrey Martinez [France] ; Evelyne Doudnikoff [France] ; Marie-Laure Martin-Négrier [France] ; Qin Chuan [République populaire de Chine] ; Bertrand Bloch [France] ; Daniel Choquet [France] ; Eric Boué-Grabot [France] ; Laurent Groc [France] ; Erwan Bezard [France, République populaire de Chine]Source :
- The Journal of Clinical Investigation [ 0021-9738 ] ; 2012.
Abstract
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DOI: 10.1172/JCI59426
PubMed: 23041629
PubMed Central: 3484432
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">PSD-95 expression controls <sc>l</sc>-DOPA dyskinesia through dopamine D1 receptor trafficking
</title><author><name sortKey="Porras, Gregory" sort="Porras, Gregory" uniqKey="Porras G" first="Gregory" last="Porras">Gregory Porras</name><affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI59426">CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>CNRS, Institut des Maladies Neurodégénératives, Bordeaux</wicri:regionArea></affiliation></author><author><name sortKey="Berthet, Amandine" sort="Berthet, Amandine" uniqKey="Berthet A" first="Amandine" last="Berthet">Amandine Berthet</name><affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI59426">CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>CNRS, Institut des Maladies Neurodégénératives, Bordeaux</wicri:regionArea></affiliation></author><author><name sortKey="Dehay, Benjamin" sort="Dehay, Benjamin" uniqKey="Dehay B" first="Benjamin" last="Dehay">Benjamin Dehay</name><affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI59426">CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>CNRS, Institut des Maladies Neurodégénératives, Bordeaux</wicri:regionArea></affiliation></author><author><name sortKey="Li, Qin" sort="Li, Qin" uniqKey="Li Q" first="Qin" last="Li">Qin Li</name><affiliation wicri:level="1"><nlm:aff id="JCI59426">Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing, China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Ladepeche, Laurent" sort="Ladepeche, Laurent" uniqKey="Ladepeche L" first="Laurent" last="Ladepeche">Laurent Ladepeche</name><affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI59426">CNRS, Institut Interdisciplinaire des Neurosciences, Bordeaux, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>CNRS, Institut Interdisciplinaire des Neurosciences, Bordeaux</wicri:regionArea></affiliation></author><author><name sortKey="Normand, Elisabeth" sort="Normand, Elisabeth" uniqKey="Normand E" first="Elisabeth" last="Normand">Elisabeth Normand</name><affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI59426">CNRS, Institut Interdisciplinaire des Neurosciences, Bordeaux, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>CNRS, Institut Interdisciplinaire des Neurosciences, Bordeaux</wicri:regionArea></affiliation></author><author><name sortKey="Dovero, Sandra" sort="Dovero, Sandra" uniqKey="Dovero S" first="Sandra" last="Dovero">Sandra Dovero</name><affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI59426">CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>CNRS, Institut des Maladies Neurodégénératives, Bordeaux</wicri:regionArea></affiliation></author><author><name sortKey="Martinez, Audrey" sort="Martinez, Audrey" uniqKey="Martinez A" first="Audrey" last="Martinez">Audrey Martinez</name><affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI59426">CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>CNRS, Institut des Maladies Neurodégénératives, Bordeaux</wicri:regionArea></affiliation></author><author><name sortKey="Doudnikoff, Evelyne" sort="Doudnikoff, Evelyne" uniqKey="Doudnikoff E" first="Evelyne" last="Doudnikoff">Evelyne Doudnikoff</name><affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI59426">CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>CNRS, Institut des Maladies Neurodégénératives, Bordeaux</wicri:regionArea></affiliation></author><author><name sortKey="Martin Negrier, Marie Laure" sort="Martin Negrier, Marie Laure" uniqKey="Martin Negrier M" first="Marie-Laure" last="Martin-Négrier">Marie-Laure Martin-Négrier</name><affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI59426">CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>CNRS, Institut des Maladies Neurodégénératives, Bordeaux</wicri:regionArea></affiliation></author><author><name sortKey="Chuan, Qin" sort="Chuan, Qin" uniqKey="Chuan Q" first="Qin" last="Chuan">Qin Chuan</name><affiliation wicri:level="1"><nlm:aff id="JCI59426">Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing, China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Bloch, Bertrand" sort="Bloch, Bertrand" uniqKey="Bloch B" first="Bertrand" last="Bloch">Bertrand Bloch</name><affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI59426">CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>CNRS, Institut des Maladies Neurodégénératives, Bordeaux</wicri:regionArea></affiliation></author><author><name sortKey="Choquet, Daniel" sort="Choquet, Daniel" uniqKey="Choquet D" first="Daniel" last="Choquet">Daniel Choquet</name><affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI59426">CNRS, Institut Interdisciplinaire des Neurosciences, Bordeaux, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>CNRS, Institut Interdisciplinaire des Neurosciences, Bordeaux</wicri:regionArea></affiliation></author><author><name sortKey="Boue Grabot, Eric" sort="Boue Grabot, Eric" uniqKey="Boue Grabot E" first="Eric" last="Boué-Grabot">Eric Boué-Grabot</name><affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI59426">CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>CNRS, Institut des Maladies Neurodégénératives, Bordeaux</wicri:regionArea></affiliation></author><author><name sortKey="Groc, Laurent" sort="Groc, Laurent" uniqKey="Groc L" first="Laurent" last="Groc">Laurent Groc</name><affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI59426">CNRS, Institut Interdisciplinaire des Neurosciences, Bordeaux, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>CNRS, Institut Interdisciplinaire des Neurosciences, Bordeaux</wicri:regionArea></affiliation></author><author><name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name><affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI59426">CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>CNRS, Institut des Maladies Neurodégénératives, Bordeaux</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI59426">Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing, China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23041629</idno><idno type="pmc">3484432</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484432</idno><idno type="RBID">PMC:3484432</idno><idno type="doi">10.1172/JCI59426</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">000484</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000484</idno><idno type="wicri:Area/Pmc/Curation">000481</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000481</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">PSD-95 expression controls <sc>l</sc>-DOPA dyskinesia through dopamine D1 receptor trafficking
</title><author><name sortKey="Porras, Gregory" sort="Porras, Gregory" uniqKey="Porras G" first="Gregory" last="Porras">Gregory Porras</name><affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI59426">CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>CNRS, Institut des Maladies Neurodégénératives, Bordeaux</wicri:regionArea></affiliation></author><author><name sortKey="Berthet, Amandine" sort="Berthet, Amandine" uniqKey="Berthet A" first="Amandine" last="Berthet">Amandine Berthet</name><affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI59426">CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>CNRS, Institut des Maladies Neurodégénératives, Bordeaux</wicri:regionArea></affiliation></author><author><name sortKey="Dehay, Benjamin" sort="Dehay, Benjamin" uniqKey="Dehay B" first="Benjamin" last="Dehay">Benjamin Dehay</name><affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI59426">CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>CNRS, Institut des Maladies Neurodégénératives, Bordeaux</wicri:regionArea></affiliation></author><author><name sortKey="Li, Qin" sort="Li, Qin" uniqKey="Li Q" first="Qin" last="Li">Qin Li</name><affiliation wicri:level="1"><nlm:aff id="JCI59426">Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing, China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Ladepeche, Laurent" sort="Ladepeche, Laurent" uniqKey="Ladepeche L" first="Laurent" last="Ladepeche">Laurent Ladepeche</name><affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI59426">CNRS, Institut Interdisciplinaire des Neurosciences, Bordeaux, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>CNRS, Institut Interdisciplinaire des Neurosciences, Bordeaux</wicri:regionArea></affiliation></author><author><name sortKey="Normand, Elisabeth" sort="Normand, Elisabeth" uniqKey="Normand E" first="Elisabeth" last="Normand">Elisabeth Normand</name><affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI59426">CNRS, Institut Interdisciplinaire des Neurosciences, Bordeaux, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>CNRS, Institut Interdisciplinaire des Neurosciences, Bordeaux</wicri:regionArea></affiliation></author><author><name sortKey="Dovero, Sandra" sort="Dovero, Sandra" uniqKey="Dovero S" first="Sandra" last="Dovero">Sandra Dovero</name><affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI59426">CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>CNRS, Institut des Maladies Neurodégénératives, Bordeaux</wicri:regionArea></affiliation></author><author><name sortKey="Martinez, Audrey" sort="Martinez, Audrey" uniqKey="Martinez A" first="Audrey" last="Martinez">Audrey Martinez</name><affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI59426">CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>CNRS, Institut des Maladies Neurodégénératives, Bordeaux</wicri:regionArea></affiliation></author><author><name sortKey="Doudnikoff, Evelyne" sort="Doudnikoff, Evelyne" uniqKey="Doudnikoff E" first="Evelyne" last="Doudnikoff">Evelyne Doudnikoff</name><affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI59426">CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>CNRS, Institut des Maladies Neurodégénératives, Bordeaux</wicri:regionArea></affiliation></author><author><name sortKey="Martin Negrier, Marie Laure" sort="Martin Negrier, Marie Laure" uniqKey="Martin Negrier M" first="Marie-Laure" last="Martin-Négrier">Marie-Laure Martin-Négrier</name><affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI59426">CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>CNRS, Institut des Maladies Neurodégénératives, Bordeaux</wicri:regionArea></affiliation></author><author><name sortKey="Chuan, Qin" sort="Chuan, Qin" uniqKey="Chuan Q" first="Qin" last="Chuan">Qin Chuan</name><affiliation wicri:level="1"><nlm:aff id="JCI59426">Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing, China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Bloch, Bertrand" sort="Bloch, Bertrand" uniqKey="Bloch B" first="Bertrand" last="Bloch">Bertrand Bloch</name><affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI59426">CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>CNRS, Institut des Maladies Neurodégénératives, Bordeaux</wicri:regionArea></affiliation></author><author><name sortKey="Choquet, Daniel" sort="Choquet, Daniel" uniqKey="Choquet D" first="Daniel" last="Choquet">Daniel Choquet</name><affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI59426">CNRS, Institut Interdisciplinaire des Neurosciences, Bordeaux, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>CNRS, Institut Interdisciplinaire des Neurosciences, Bordeaux</wicri:regionArea></affiliation></author><author><name sortKey="Boue Grabot, Eric" sort="Boue Grabot, Eric" uniqKey="Boue Grabot E" first="Eric" last="Boué-Grabot">Eric Boué-Grabot</name><affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI59426">CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>CNRS, Institut des Maladies Neurodégénératives, Bordeaux</wicri:regionArea></affiliation></author><author><name sortKey="Groc, Laurent" sort="Groc, Laurent" uniqKey="Groc L" first="Laurent" last="Groc">Laurent Groc</name><affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI59426">CNRS, Institut Interdisciplinaire des Neurosciences, Bordeaux, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>CNRS, Institut Interdisciplinaire des Neurosciences, Bordeaux</wicri:regionArea></affiliation></author><author><name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name><affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI59426">CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>CNRS, Institut des Maladies Neurodégénératives, Bordeaux</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI59426">Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing, China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing</wicri:regionArea></affiliation></author></analytic><series><title level="j">The Journal of Clinical Investigation</title><idno type="ISSN">0021-9738</idno><idno type="eISSN">1558-8238</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><sc>l</sc>-DOPA–induced dyskinesia (LID), a detrimental consequence of dopamine replacement therapy for Parkinson’s disease, is associated with an alteration in dopamine D1 receptor (D1R) and glutamate receptor interactions. We hypothesized that the synaptic scaffolding protein PSD-95 plays a pivotal role in this process, as it interacts with D1R, regulates its trafficking and function, and is overexpressed in LID. Here, we demonstrate in rat and macaque models that disrupting the interaction between D1R and PSD-95 in the striatum reduces LID development and severity. Single quantum dot imaging revealed that this benefit was achieved primarily by destabilizing D1R localization, via increased lateral diffusion followed by increased internalization and diminished surface expression. These findings indicate that altering D1R trafficking via synapse-associated scaffolding proteins may be useful in the treatment of dyskinesia in Parkinson’s patients.
</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 Clin Invest</journal-id><journal-id journal-id-type="iso-abbrev">J. Clin. Invest</journal-id><journal-id journal-id-type="publisher-id">J CLIN INVEST</journal-id><journal-title-group><journal-title>The Journal of Clinical Investigation</journal-title></journal-title-group><issn pub-type="ppub">0021-9738</issn><issn pub-type="epub">1558-8238</issn><publisher><publisher-name>American Society for Clinical Investigation</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23041629</article-id><article-id pub-id-type="pmc">3484432</article-id><article-id pub-id-type="publisher-id">59426</article-id><article-id pub-id-type="doi">10.1172/JCI59426</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>PSD-95 expression controls <sc>l</sc>-DOPA dyskinesia through dopamine D1 receptor trafficking
</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Porras</surname><given-names>Gregory</given-names></name><xref ref-type="aff" rid="JCI59426">1</xref><xref ref-type="aff" rid="JCI59426">2</xref></contrib><contrib contrib-type="author"><name><surname>Berthet</surname><given-names>Amandine</given-names></name><xref ref-type="aff" rid="JCI59426">1</xref><xref ref-type="aff" rid="JCI59426">2</xref></contrib><contrib contrib-type="author"><name><surname>Dehay</surname><given-names>Benjamin</given-names></name><xref ref-type="aff" rid="JCI59426">1</xref><xref ref-type="aff" rid="JCI59426">2</xref></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Qin</given-names></name><xref ref-type="aff" rid="JCI59426">3</xref></contrib><contrib contrib-type="author"><name><surname>Ladepeche</surname><given-names>Laurent</given-names></name><xref ref-type="aff" rid="JCI59426">4</xref><xref ref-type="aff" rid="JCI59426">5</xref></contrib><contrib contrib-type="author"><name><surname>Normand</surname><given-names>Elisabeth</given-names></name><xref ref-type="aff" rid="JCI59426">4</xref><xref ref-type="aff" rid="JCI59426">5</xref></contrib><contrib contrib-type="author"><name><surname>Dovero</surname><given-names>Sandra</given-names></name><xref ref-type="aff" rid="JCI59426">1</xref><xref ref-type="aff" rid="JCI59426">2</xref></contrib><contrib contrib-type="author"><name><surname>Martinez</surname><given-names>Audrey</given-names></name><xref ref-type="aff" rid="JCI59426">1</xref><xref ref-type="aff" rid="JCI59426">2</xref></contrib><contrib contrib-type="author"><name><surname>Doudnikoff</surname><given-names>Evelyne</given-names></name><xref ref-type="aff" rid="JCI59426">1</xref><xref ref-type="aff" rid="JCI59426">2</xref></contrib><contrib contrib-type="author"><name><surname>Martin-Négrier</surname><given-names>Marie-Laure</given-names></name><xref ref-type="aff" rid="JCI59426">1</xref><xref ref-type="aff" rid="JCI59426">2</xref></contrib><contrib contrib-type="author"><name><surname>Chuan</surname><given-names>Qin</given-names></name><xref ref-type="aff" rid="JCI59426">3</xref></contrib><contrib contrib-type="author"><name><surname>Bloch</surname><given-names>Bertrand</given-names></name><xref ref-type="aff" rid="JCI59426">1</xref><xref ref-type="aff" rid="JCI59426">2</xref></contrib><contrib contrib-type="author"><name><surname>Choquet</surname><given-names>Daniel</given-names></name><xref ref-type="aff" rid="JCI59426">4</xref><xref ref-type="aff" rid="JCI59426">5</xref></contrib><contrib contrib-type="author"><name><surname>Boué-Grabot</surname><given-names>Eric</given-names></name><xref ref-type="aff" rid="JCI59426">1</xref><xref ref-type="aff" rid="JCI59426">2</xref></contrib><contrib contrib-type="author"><name><surname>Groc</surname><given-names>Laurent</given-names></name><xref ref-type="aff" rid="JCI59426">4</xref><xref ref-type="aff" rid="JCI59426">5</xref></contrib><contrib contrib-type="author"><name><surname>Bezard</surname><given-names>Erwan</given-names></name><xref ref-type="aff" rid="JCI59426">1</xref><xref ref-type="aff" rid="JCI59426">2</xref><xref ref-type="aff" rid="JCI59426">3</xref></contrib></contrib-group><aff id="JCI59426"><label>1</label>Université de Bordeaux and<label>2</label>CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.<label>3</label>Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing, China.<label>4</label>Université de Bordeaux and<label>5</label>CNRS, Institut Interdisciplinaire des Neurosciences, Bordeaux, France.</aff><author-notes><corresp>Address correspondence to: Erwan Bezard, CNRS UMR 5293, IMN, Université Bordeaux Segalen, 146 rue Léo Saignat, 33076 Bordeaux cedex, France. Phone: 5575.71687; Fax: 5569.86182; E-mail:
<email>erwan.bezard@u-bordeaux2.fr</email>.
</corresp><fn><p><bold>Authorship note:</bold> Gregory Porras and Amandine Berthet are co–first authors. Laurent Groc and Erwan Bezard are co–senior authors.
</p></fn></author-notes><pub-date pub-type="epub"><day>8</day><month>10</month><year>2012</year></pub-date><pub-date pub-type="ppub"><day>1</day><month>11</month><year>2012</year></pub-date><pub-date pub-type="pmc-release"><day>8</day><month>10</month><year>2012</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>122</volume><issue>11</issue><fpage>3977</fpage><lpage>3989</lpage><history><date date-type="received"><day>2</day><month>5</month><year>2012</year></date><date date-type="accepted"><day>16</day><month>8</month><year>2012</year></date></history><permissions><copyright-statement>Copyright © 2012, American Society for Clinical Investigation</copyright-statement><copyright-year>2012</copyright-year></permissions><abstract><p><sc>l</sc>-DOPA–induced dyskinesia (LID), a detrimental consequence of dopamine replacement therapy for Parkinson’s disease, is associated with an alteration in dopamine D1 receptor (D1R) and glutamate receptor interactions. We hypothesized that the synaptic scaffolding protein PSD-95 plays a pivotal role in this process, as it interacts with D1R, regulates its trafficking and function, and is overexpressed in LID. Here, we demonstrate in rat and macaque models that disrupting the interaction between D1R and PSD-95 in the striatum reduces LID development and severity. Single quantum dot imaging revealed that this benefit was achieved primarily by destabilizing D1R localization, via increased lateral diffusion followed by increased internalization and diminished surface expression. These findings indicate that altering D1R trafficking via synapse-associated scaffolding proteins may be useful in the treatment of dyskinesia in Parkinson’s patients.
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