{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T03:25:23Z","timestamp":1791170723296,"version":"4.1.0"},"reference-count":26,"publisher":"National Academy of Sciences","issue":"37","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,9,16]]},"abstract":"<jats:p>\n                    The\n                    <jats:italic>Caenorhabditis elegans (C. elegans)<\/jats:italic>\n                    dopamine (DA) transporter (DAT-1) regulates DA signaling through efficient DA reuptake following synaptic release. In addition to its DA transport function, DAT-1 generates detectible DA-gated currents that may influence neuronal excitability. Previously, we provided evidence that single Cl-channel events underlie DAT-1 currents. In these studies, we identified a distinct population of altered DAT-1 currents arising from DAT-1 transgenic constructs bearing an N-terminal GFP fusion. The presence of these channels suggested disruption of an endogenous regulatory mechanism that modulates occupancy of DAT-1 channel states. A leading candidate for such a regulator is the SNARE protein syntaxin 1A (Syn1A), previously found to interact with homologous transporters through N-terminal interactions. Here we establish that UNC-64 (\n                    <jats:italic>C. elegans<\/jats:italic>\n                    Syn1A homologue) associates with DAT-1 and suppresses transporter channel properties. In contrast, GFP::DAT-1 is unable to form stable transporter\/UNC-64 complexes that limit channel states. Although DAT-1 and GFP::DAT-1 expressing DA neurons exhibit comparable DA uptake, GFP::DAT-1 animals exhibit swimming-induced paralysis (SWIP), a phenotype associated with excess synaptic DA release and spillover. We propose that loss of UNC-64\/DAT-1 interactions leads to enhanced synaptic DA release, providing a novel mechanism for DA neuron sensitization that may be relevant to mechanisms of DA-associated disorders.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0802214105","type":"journal-article","created":{"date-parts":[[2008,9,3]],"date-time":"2008-09-03T20:53:59Z","timestamp":1220475239000},"page":"14192-14197","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":80,"title":["Dopamine transporter\/syntaxin 1A interactions regulate transporter channel activity and dopaminergic synaptic transmission"],"prefix":"10.1073","volume":"105","author":[{"given":"Lucia","family":"Carvelli","sequence":"first","affiliation":[{"name":"Departments of *Pharmacology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randy D.","family":"Blakely","sequence":"additional","affiliation":[{"name":"Departments of *Pharmacology and"},{"name":"Psychiatry and Center for Molecular Neuroscience, Vanderbilt University School of Medicine, Nashville, TN 37232-8548"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis J.","family":"DeFelice","sequence":"additional","affiliation":[{"name":"Departments of *Pharmacology and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2008,9,16]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn920"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403299101"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(96)79506-1"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.22.13260"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90159-0"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.2.723"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-19-07561.2001"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407737102"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.12.049"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/375645a0"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/3-540-29784-7_9"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-05-01697.2003"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00605-6"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/79939"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/36882"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/378623a0"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1023\/B:NERE.0000026404.08779.43"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2992-07.2007"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C300349200"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M201926200"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/379606a0"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2004.03.008"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/77.1.71"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/cm.970200108"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/131.3.609"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.042497999"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0802214105","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T17:01:27Z","timestamp":1649782887000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0802214105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,9,16]]},"references-count":26,"journal-issue":{"issue":"37","published-print":{"date-parts":[[2008,9,16]]}},"alternative-id":["10.1073\/pnas.0802214105"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0802214105","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1123369.580529","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,9,16]]},"assertion":[{"value":"2008-03-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-09-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}