Functional Homomers and Heteromers of Dopamine D2L and D3 Receptors Co-exist at the Cell Surface
Identifieur interne : 000615 ( Pmc/Checkpoint ); précédent : 000614; suivant : 000616Functional Homomers and Heteromers of Dopamine D2L and D3 Receptors Co-exist at the Cell Surface
Auteurs : Chantevy Pou ; Clotilde Mannoury La Cour ; Leigh A. Stoddart ; Mark J. Millan ; Graeme MilliganSource :
- The Journal of Biological Chemistry [ 0021-9258 ] ; 2012.
Abstract
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DOI: 10.1074/jbc.M111.326678
PubMed: 22291025
PubMed Central: 3308812
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Functional Homomers and Heteromers of Dopamine D<sub>2L</sub> and D<sub>3</sub> Receptors Co-exist at the Cell Surface<xref ref-type="fn" rid="FN1"><sup><inline-graphic xlink:href="sbox.jpg"></inline-graphic></sup></xref></title><author><name sortKey="Pou, Chantevy" sort="Pou, Chantevy" uniqKey="Pou C" first="Chantevy" last="Pou">Chantevy Pou</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Mannoury La Cour, Clotilde" sort="Mannoury La Cour, Clotilde" uniqKey="Mannoury La Cour C" first="Clotilde" last="Mannoury La Cour">Clotilde Mannoury La Cour</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Stoddart, Leigh A" sort="Stoddart, Leigh A" uniqKey="Stoddart L" first="Leigh A." last="Stoddart">Leigh A. Stoddart</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Millan, Mark J" sort="Millan, Mark J" uniqKey="Millan M" first="Mark J." last="Millan">Mark J. Millan</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Milligan, Graeme" sort="Milligan, Graeme" uniqKey="Milligan G" first="Graeme" last="Milligan">Graeme Milligan</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22291025</idno><idno type="pmc">3308812</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308812</idno><idno type="RBID">PMC:3308812</idno><idno type="doi">10.1074/jbc.M111.326678</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">000472</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000472</idno><idno type="wicri:Area/Pmc/Curation">000469</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000469</idno><idno type="wicri:Area/Pmc/Checkpoint">000615</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000615</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Functional Homomers and Heteromers of Dopamine D<sub>2L</sub> and D<sub>3</sub> Receptors Co-exist at the Cell Surface<xref ref-type="fn" rid="FN1"><sup><inline-graphic xlink:href="sbox.jpg"></inline-graphic></sup></xref></title><author><name sortKey="Pou, Chantevy" sort="Pou, Chantevy" uniqKey="Pou C" first="Chantevy" last="Pou">Chantevy Pou</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Mannoury La Cour, Clotilde" sort="Mannoury La Cour, Clotilde" uniqKey="Mannoury La Cour C" first="Clotilde" last="Mannoury La Cour">Clotilde Mannoury La Cour</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Stoddart, Leigh A" sort="Stoddart, Leigh A" uniqKey="Stoddart L" first="Leigh A." last="Stoddart">Leigh A. Stoddart</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Millan, Mark J" sort="Millan, Mark J" uniqKey="Millan M" first="Mark J." last="Millan">Mark J. Millan</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Milligan, Graeme" sort="Milligan, Graeme" uniqKey="Milligan G" first="Graeme" last="Milligan">Graeme Milligan</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="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><bold>Background:</bold> Dopamine D<sub>2</sub> and D<sub>3</sub> receptor subtypes are often co-expressed.</p><p><bold>Results:</bold> Systems were established to allow concurrent detection of receptor homomers and heteromers.</p><p><bold>Conclusion:</bold> Co-expressed D<sub>2</sub> and D<sub>3</sub> receptors form both homomers and heteromers and all are functional and present concurrently.</p><p><bold>Significance:</bold> These observations are relevant to the pathogenesis and treatment of disorders in which D<sub>2</sub> and D<sub>3</sub> receptors are implicated.</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>9650 Rockville Pike, Bethesda, MD 20814, U.S.A.</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">22291025</article-id><article-id pub-id-type="pmc">3308812</article-id><article-id pub-id-type="publisher-id">M111.326678</article-id><article-id pub-id-type="doi">10.1074/jbc.M111.326678</article-id><article-categories><subj-group subj-group-type="heading"><subject>Signal Transduction</subject></subj-group></article-categories><title-group><article-title>Functional Homomers and Heteromers of Dopamine D<sub>2L</sub> and D<sub>3</sub> Receptors Co-exist at the Cell Surface<xref ref-type="fn" rid="FN1"><sup><inline-graphic xlink:href="sbox.jpg"></inline-graphic></sup></xref></article-title><alt-title alt-title-type="short">Coexistence of Dopamine Receptor Homo- and Heteromers</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Pou</surname><given-names>Chantevy</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Mannoury la Cour</surname><given-names>Clotilde</given-names></name><xref ref-type="aff" rid="aff2"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Stoddart</surname><given-names>Leigh A.</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="author-notes" rid="FN2"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Millan</surname><given-names>Mark J.</given-names></name><xref ref-type="aff" rid="aff2"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Milligan</surname><given-names>Graeme</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="corresp" rid="cor1"><sup>2</sup></xref></contrib><aff id="aff1">From the<label>‡</label>Molecular Pharmacology Group, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom G12 8QQ and</aff><aff id="aff2">the<label>§</label>Institut de Recherches Servier, Unité de Recherche et découverte en Neurosciences, 125 Chemin de Ronde, Croissy sur Seine, France 78290</aff></contrib-group><author-notes><corresp id="cor1"><label>2</label> To whom correspondence should be addressed. Tel.: <phone>44-141-330-5557</phone>; Fax: <fax>44-141-330-5481</fax>; E-mail: <email>Graeme.Milligan@glasgow.ac.uk</email>.</corresp><fn fn-type="present-address" id="FN2"><label>1</label><p>Present address: Institute for Cellular Signalling, University of Nottingham, Nottingham, U.K.</p></fn></author-notes><pub-date pub-type="ppub"><day>16</day><month>3</month><year>2012</year></pub-date><pub-date pub-type="epub"><day>30</day><month>1</month><year>2012</year></pub-date><volume>287</volume><issue>12</issue><fpage>8864</fpage><lpage>8878</lpage><history><date date-type="received"><day>22</day><month>11</month><year>2011</year></date><date date-type="rev-recd"><day>26</day><month>1</month><year>2012</year></date></history><permissions><copyright-statement>© 2012 by The American Society for Biochemistry and Molecular Biology, Inc.</copyright-statement><copyright-year>2012</copyright-year></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zbc01212008864.pdf"></self-uri><abstract abstract-type="teaser"><p><bold>Background:</bold> Dopamine D<sub>2</sub> and D<sub>3</sub> receptor subtypes are often co-expressed.</p><p><bold>Results:</bold> Systems were established to allow concurrent detection of receptor homomers and heteromers.</p><p><bold>Conclusion:</bold> Co-expressed D<sub>2</sub> and D<sub>3</sub> receptors form both homomers and heteromers and all are functional and present concurrently.</p><p><bold>Significance:</bold> These observations are relevant to the pathogenesis and treatment of disorders in which D<sub>2</sub> and D<sub>3</sub> receptors are implicated.</p></abstract><abstract><p>Human dopamine D<sub>2long</sub> and D<sub>3</sub> receptors were modified by N-terminal addition of SNAP or CLIP forms of <italic>O</italic><sup>6</sup>-alkylguanine-DNA-alkyltransferase plus a peptide epitope tag. Cells able to express each of these four constructs only upon addition of an antibiotic were established and used to confirm regulated and inducible control of expression, the specificity of SNAP and CLIP tag covalent labeling reagents, and based on homogenous time-resolved fluorescence resonance energy transfer, the presence of cell surface D<sub>2long</sub> and D<sub>3</sub> receptor homomers. Following constitutive expression of reciprocal constructs, potentially capable of forming and reporting the presence of cell surface D<sub>2long</sub>-D<sub>3</sub> heteromers, individual clones were assessed for levels of expression of the constitutively expressed protomer. This was unaffected by induction of the partner protomer and the level of expression of the partner required to generate detectable cell surface D<sub>2long</sub>–D<sub>3</sub> heteromers was defined. Such homomers and heteromers were found to co-exist and using a reconstitution of function approach both homomers and heteromers of D<sub>2long</sub> and D<sub>3</sub> receptors were shown to be functional, potentially via trans-activation of associated G protein. These studies demonstrate the ability of dopamine D<sub>2long</sub> and D<sub>3</sub> receptors to form both homomers and heteromers, and show that in cells expressing each subtype a complex mixture of homomers and heteromers co-exists at steady state. These data are of potential importance both to disorders in which D<sub>2long</sub> and D<sub>3</sub> receptors are implicated, like schizophrenia and Parkinson disease, and also to drugs exerting their actions via these sites.</p></abstract><kwd-group><kwd>7-Helix receptor</kwd><kwd>Dopamine</kwd><kwd>Fluorescence Resonance Energy Transfer (FRET)</kwd><kwd>G Protein-coupled Receptors (GPCR)</kwd><kwd>G Proteins</kwd></kwd-group></article-meta></front></pmc><affiliations><list></list><tree><noCountry><name sortKey="Mannoury La Cour, Clotilde" sort="Mannoury La Cour, Clotilde" uniqKey="Mannoury La Cour C" first="Clotilde" last="Mannoury La Cour">Clotilde Mannoury La Cour</name><name sortKey="Millan, Mark J" sort="Millan, Mark J" uniqKey="Millan M" first="Mark J." last="Millan">Mark J. Millan</name><name sortKey="Milligan, Graeme" sort="Milligan, Graeme" uniqKey="Milligan G" first="Graeme" last="Milligan">Graeme Milligan</name><name sortKey="Pou, Chantevy" sort="Pou, Chantevy" uniqKey="Pou C" first="Chantevy" last="Pou">Chantevy Pou</name><name sortKey="Stoddart, Leigh A" sort="Stoddart, Leigh A" uniqKey="Stoddart L" first="Leigh A." last="Stoddart">Leigh A. Stoddart</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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