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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Ctr9, a Protein in the Transcription Complex Paf1, Regulates Dopamine Transporter Activity at the Plasma Membrane<xref ref-type="fn" rid="FN1">*</xref>
</title>
<author><name sortKey="De Gois, Stephanie" sort="De Gois, Stephanie" uniqKey="De Gois S" first="Stéphanie" last="De Gois">Stéphanie De Gois</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">CNRS UMR 7224, 75005 Paris, France,</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff3">Université Pierre et Marie Curie, Neuroscience Paris Seine, 75005 Paris, France,</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff4">Douglas Hospital Research Center, Department of Psychiatry, McGill University, Montreal H4H 1R3 Quebec, Canada,</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Slama, Patrick" sort="Slama, Patrick" uniqKey="Slama P" first="Patrick" last="Slama">Patrick Slama</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">CNRS UMR 7224, 75005 Paris, France,</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff3">Université Pierre et Marie Curie, Neuroscience Paris Seine, 75005 Paris, France,</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Pietrancosta, Nicolas" sort="Pietrancosta, Nicolas" uniqKey="Pietrancosta N" first="Nicolas" last="Pietrancosta">Nicolas Pietrancosta</name>
<affiliation><nlm:aff id="aff5">Université Paris Descartes, Sorbonne Paris Cité,</nlm:aff>
</affiliation>
<affiliation><nlm:aff wicri:cut=", and" id="aff6">CNRS, UMR 8601, 75006 Paris, France</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Erdozain, Amaia M" sort="Erdozain, Amaia M" uniqKey="Erdozain A" first="Amaia M." last="Erdozain">Amaia M. Erdozain</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">CNRS UMR 7224, 75005 Paris, France,</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff3">Université Pierre et Marie Curie, Neuroscience Paris Seine, 75005 Paris, France,</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Louis, Franck" sort="Louis, Franck" uniqKey="Louis F" first="Franck" last="Louis">Franck Louis</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">CNRS UMR 7224, 75005 Paris, France,</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff3">Université Pierre et Marie Curie, Neuroscience Paris Seine, 75005 Paris, France,</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bouvrais Veret, Caroline" sort="Bouvrais Veret, Caroline" uniqKey="Bouvrais Veret C" first="Caroline" last="Bouvrais-Veret">Caroline Bouvrais-Veret</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">CNRS UMR 7224, 75005 Paris, France,</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff3">Université Pierre et Marie Curie, Neuroscience Paris Seine, 75005 Paris, France,</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Daviet, Laurent" sort="Daviet, Laurent" uniqKey="Daviet L" first="Laurent" last="Daviet">Laurent Daviet</name>
<affiliation><nlm:aff id="aff7">Hybrigenics, 3–5 Impasse Reille, 75014 Paris, France</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Giros, Bruno" sort="Giros, Bruno" uniqKey="Giros B" first="Bruno" last="Giros">Bruno Giros</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">CNRS UMR 7224, 75005 Paris, France,</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff3">Université Pierre et Marie Curie, Neuroscience Paris Seine, 75005 Paris, France,</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff4">Douglas Hospital Research Center, Department of Psychiatry, McGill University, Montreal H4H 1R3 Quebec, Canada,</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">26048990</idno>
<idno type="pmc">4505035</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505035</idno>
<idno type="RBID">PMC:4505035</idno>
<idno type="doi">10.1074/jbc.M115.646315</idno>
<date when="2015">2015</date>
<idno type="wicri:Area/Pmc/Corpus">000037</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000037</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Ctr9, a Protein in the Transcription Complex Paf1, Regulates Dopamine Transporter Activity at the Plasma Membrane<xref ref-type="fn" rid="FN1">*</xref>
</title>
<author><name sortKey="De Gois, Stephanie" sort="De Gois, Stephanie" uniqKey="De Gois S" first="Stéphanie" last="De Gois">Stéphanie De Gois</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">CNRS UMR 7224, 75005 Paris, France,</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff3">Université Pierre et Marie Curie, Neuroscience Paris Seine, 75005 Paris, France,</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff4">Douglas Hospital Research Center, Department of Psychiatry, McGill University, Montreal H4H 1R3 Quebec, Canada,</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Slama, Patrick" sort="Slama, Patrick" uniqKey="Slama P" first="Patrick" last="Slama">Patrick Slama</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">CNRS UMR 7224, 75005 Paris, France,</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff3">Université Pierre et Marie Curie, Neuroscience Paris Seine, 75005 Paris, France,</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Pietrancosta, Nicolas" sort="Pietrancosta, Nicolas" uniqKey="Pietrancosta N" first="Nicolas" last="Pietrancosta">Nicolas Pietrancosta</name>
<affiliation><nlm:aff id="aff5">Université Paris Descartes, Sorbonne Paris Cité,</nlm:aff>
</affiliation>
<affiliation><nlm:aff wicri:cut=", and" id="aff6">CNRS, UMR 8601, 75006 Paris, France</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Erdozain, Amaia M" sort="Erdozain, Amaia M" uniqKey="Erdozain A" first="Amaia M." last="Erdozain">Amaia M. Erdozain</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">CNRS UMR 7224, 75005 Paris, France,</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff3">Université Pierre et Marie Curie, Neuroscience Paris Seine, 75005 Paris, France,</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Louis, Franck" sort="Louis, Franck" uniqKey="Louis F" first="Franck" last="Louis">Franck Louis</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">CNRS UMR 7224, 75005 Paris, France,</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff3">Université Pierre et Marie Curie, Neuroscience Paris Seine, 75005 Paris, France,</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bouvrais Veret, Caroline" sort="Bouvrais Veret, Caroline" uniqKey="Bouvrais Veret C" first="Caroline" last="Bouvrais-Veret">Caroline Bouvrais-Veret</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">CNRS UMR 7224, 75005 Paris, France,</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff3">Université Pierre et Marie Curie, Neuroscience Paris Seine, 75005 Paris, France,</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Daviet, Laurent" sort="Daviet, Laurent" uniqKey="Daviet L" first="Laurent" last="Daviet">Laurent Daviet</name>
<affiliation><nlm:aff id="aff7">Hybrigenics, 3–5 Impasse Reille, 75014 Paris, France</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Giros, Bruno" sort="Giros, Bruno" uniqKey="Giros B" first="Bruno" last="Giros">Bruno Giros</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">CNRS UMR 7224, 75005 Paris, France,</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff3">Université Pierre et Marie Curie, Neuroscience Paris Seine, 75005 Paris, France,</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff4">Douglas Hospital Research Center, Department of Psychiatry, McGill University, Montreal H4H 1R3 Quebec, Canada,</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><bold>Background:</bold>
The dopamine transporter controls the concentration of dopamine at the synapse.</p>
<p><bold>Results:</bold>
Ctr9, formerly identified as a nuclei protein, interacts with the dopamine transporter in the cytoplasmic compartment.</p>
<p><bold>Conclusion:</bold>
This interaction facilitates the targeting of the dopamine transporter to the plasma membrane and increases its activity.</p>
<p><bold>Significance:</bold>
Identifying the complete dopamine transporter interactome is essential to understanding how neurotransmission is regulated.</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">26048990</article-id>
<article-id pub-id-type="pmc">4505035</article-id>
<article-id pub-id-type="publisher-id">M115.646315</article-id>
<article-id pub-id-type="doi">10.1074/jbc.M115.646315</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Neurobiology</subject>
</subj-group>
</article-categories>
<title-group><article-title>Ctr9, a Protein in the Transcription Complex Paf1, Regulates Dopamine Transporter Activity at the Plasma Membrane<xref ref-type="fn" rid="FN1">*</xref>
</article-title>
<alt-title alt-title-type="short">Regulation of DAT Function by a New Partner: Ctr9</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>De Gois</surname>
<given-names>Stéphanie</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>‡</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>§</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>¶</sup>
</xref>
<xref ref-type="aff" rid="aff4"><sup>‖</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Slama</surname>
<given-names>Patrick</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>‡</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>§</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>¶</sup>
</xref>
<xref ref-type="author-notes" rid="FN2"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pietrancosta</surname>
<given-names>Nicolas</given-names>
</name>
<xref ref-type="aff" rid="aff5">**</xref>
<xref ref-type="aff" rid="aff6"><sup>‡‡</sup>
</xref>
<xref ref-type="author-notes" rid="FN2"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Erdozain</surname>
<given-names>Amaia M.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>‡</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>§</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>¶</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Louis</surname>
<given-names>Franck</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>‡</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>§</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>¶</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bouvrais-Veret</surname>
<given-names>Caroline</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>‡</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>§</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>¶</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Daviet</surname>
<given-names>Laurent</given-names>
</name>
<xref ref-type="aff" rid="aff7"><sup>§§</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Giros</surname>
<given-names>Bruno</given-names>
</name>
<contrib-id contrib-id-type="orcid">http://orcid.org/0000-0001-5876-9822</contrib-id>
<xref ref-type="aff" rid="aff1"><sup>‡</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>§</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>¶</sup>
</xref>
<xref ref-type="aff" rid="aff4"><sup>‖</sup>
</xref>
<xref ref-type="corresp" rid="cor1"><sup>2</sup>
</xref>
</contrib>
<aff id="aff1">From the<label>‡</label>
INSERM U952 and</aff>
<aff id="aff2"><label>§</label>
CNRS UMR 7224, 75005 Paris, France,</aff>
<aff id="aff3"><label>¶</label>
Université Pierre et Marie Curie, Neuroscience Paris Seine, 75005 Paris, France,</aff>
<aff id="aff4"><label>‖</label>
Douglas Hospital Research Center, Department of Psychiatry, McGill University, Montreal H4H 1R3 Quebec, Canada,</aff>
<aff id="aff5"><label>**</label>
Université Paris Descartes, Sorbonne Paris Cité,</aff>
<aff id="aff6"><label>‡‡</label>
CNRS, UMR 8601, 75006 Paris, France, and</aff>
<aff id="aff7"><label>§§</label>
Hybrigenics, 3–5 Impasse Reille, 75014 Paris, France</aff>
</contrib-group>
<author-notes><corresp id="cor1"><label>2</label>
To whom correspondence should be addressed: <addr-line>Douglas Hospital Research Center, Department of Psychiatry, McGill University, Montreal H4H 1R3 Quebec, Canada.</addr-line>
Tel.: <phone>514-261-0520</phone>
; Fax: <fax>514-762-3034</fax>
; E-mail: <email>bruno.giros@mcgill.ca</email>
or <email>bruno.giros@upmc.fr</email>
.</corresp>
<fn fn-type="equal" id="FN2"><label>1</label>
<p>Both authors contributed equally to this work.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><day>17</day>
<month>7</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="epub"><day>5</day>
<month>6</month>
<year>2015</year>
</pub-date>
<volume>290</volume>
<issue>29</issue>
<fpage>17848</fpage>
<lpage>17862</lpage>
<history><date date-type="received"><day>19</day>
<month>2</month>
<year>2015</year>
</date>
<date date-type="rev-recd"><day>27</day>
<month>5</month>
<year>2015</year>
</date>
</history>
<permissions><copyright-statement>© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.</copyright-statement>
<copyright-year>2015</copyright-year>
</permissions>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zbc02915017848.pdf"></self-uri>
<abstract abstract-type="teaser"><p><bold>Background:</bold>
The dopamine transporter controls the concentration of dopamine at the synapse.</p>
<p><bold>Results:</bold>
Ctr9, formerly identified as a nuclei protein, interacts with the dopamine transporter in the cytoplasmic compartment.</p>
<p><bold>Conclusion:</bold>
This interaction facilitates the targeting of the dopamine transporter to the plasma membrane and increases its activity.</p>
<p><bold>Significance:</bold>
Identifying the complete dopamine transporter interactome is essential to understanding how neurotransmission is regulated.</p>
</abstract>
<abstract><p>Dopamine (DA) is a major regulator of sensorimotor and cognitive functions. The DA transporter (DAT) is the key protein that regulates the spatial and temporal activity of DA release into the synaptic cleft via the rapid reuptake of DA into presynaptic termini. Several lines of evidence have suggested that transporter-interacting proteins may play a role in DAT function and regulation. Here, we identified the tetratricopeptide repeat domain-containing protein Ctr9 as a novel DAT binding partner using a yeast two-hybrid system. We showed that Ctr9 is expressed in dopaminergic neurons and forms a stable complex with DAT <italic>in vivo</italic>
via GST pulldown and co-immunoprecipitation assays. In mammalian cells co-expressing both proteins, Ctr9 partially colocalizes with DAT at the plasma membrane. This interaction between DAT and Ctr9 results in a dramatic enhancement of DAT-mediated DA uptake due to an increased number of DAT transporters at the plasma membrane. We determined that the binding of Ctr9 to DAT requires residues YKF in the first half of the DAT C terminus. In addition, we characterized Ctr9, providing new insight into this protein. Using three-dimensional modeling, we identified three novel tetratricopeptide repeat domains in the Ctr9 sequence, and based on deletion mutation experiments, we demonstrated the role of the SH2 domain of Ctr9 in nuclear localization. Our results demonstrate that Ctr9 localization is not restricted to the nucleus, as previously described for the transcription complex Paf1. Taken together, our data provide evidence that Ctr9 modulates DAT function by regulating its trafficking.</p>
</abstract>
<kwd-group><kwd>dopamine transporter</kwd>
<kwd>membrane trafficking</kwd>
<kwd>membrane transport</kwd>
<kwd>protein-protein interaction</kwd>
<kwd>transcription factor</kwd>
<kwd>membrane targeting</kwd>
<kwd>tetratricopeptide domain repeat</kwd>
<kwd>uptake activity</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>
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