Abstract
Dopamine (DA) is a neurotransmitter implicated in multiple functions, including movement, cognition, motivation, and reward. The DA transporter (DAT) is responsible for clearing extracellular DA, thereby terminating DA neurotransmission. Previously, it has been shown that insulin signaling through protein kinase B/Akt regulates DAT function by fine-tuning DAT cell surface expression. Importantly, specific Akt isoforms (e.g., Akt1, Akt2) serve distinct physiological functions. Here, we demonstrate using isoform-specific Akt inhibitors that basal activity of Akt2, rather than Akt1, regulates DAT cell surface expression. Since Akt2 activation is mediated by insulin, these data further implicate insulin signaling as an important modulator of DAT function and dopaminergic tone.
Keywords:
Akt; Dopamine; insulin; transporter.
Publication types
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Letter
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Research Support, N.I.H., Extramural
MeSH terms
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Allosteric Regulation
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Animals
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Cell Membrane / enzymology
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Corpus Striatum / cytology
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Dopamine / metabolism
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Dopamine Plasma Membrane Transport Proteins / genetics
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Dopamine Plasma Membrane Transport Proteins / metabolism*
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Dopaminergic Neurons / drug effects
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Dopaminergic Neurons / enzymology
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HEK293 Cells / drug effects
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HEK293 Cells / enzymology
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HEK293 Cells / metabolism
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Humans
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Insulin / physiology
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Isoenzymes / antagonists & inhibitors
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Isoenzymes / physiology
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Phosphorylation
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Protein Processing, Post-Translational
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Protein Transport / physiology
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Proto-Oncogene Proteins c-akt / antagonists & inhibitors
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Proto-Oncogene Proteins c-akt / physiology*
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Rats
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Rats, Sprague-Dawley
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Recombinant Fusion Proteins / metabolism
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Signal Transduction
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Substrate Specificity
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Transfection
Substances
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Dopamine Plasma Membrane Transport Proteins
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Insulin
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Isoenzymes
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Recombinant Fusion Proteins
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AKT1 protein, human
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AKT2 protein, human
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Proto-Oncogene Proteins c-akt
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Dopamine