Dopamine transporter/syntaxin 1A interactions regulate transporter channel activity and dopaminergic synaptic transmission.

Dopamine transporter/syntaxin 1A interactions regulate transporter channel activity and dopaminergic synaptic transmission. Research Abstract Details 

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Dopamine transporter/syntaxin 1A interactions regulate transporter channel activity and dopaminergic synaptic transmission. Abstract Text:

The Caenorhabditis elegans (C. elegans) 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 (C. elegans 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.

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Dopamine transporter/syntaxin 1A interactions regulate transporter channel activity and dopaminergic synaptic transmission. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 105

Page Numbers: 14192-7

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 1091-6490

DAY: 3

MONTH: 09

YEAR: 2008

Dopamine transporter/syntaxin 1A interactions regulate transporter channel activity and dopaminergic synaptic transmission. Information

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LANGUAGE: eng

NlmUniqueID: 7505876

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Grant and Affiliation Information for Dopamine transporter/syntaxin 1A interactions regulate transporter channel activity and dopaminergic synaptic transmission.

AFFILIATION: Departments of Pharmacology and Psychiatry and Center for Molecular Neuroscience, Vanderbilt University School of Medicine, Nashville, TN 37232-8548.

Country: United States

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MEDLINETA: Proc Natl Acad Sci U S A

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