Akt-dependent and isoform-specific regulation of dopamine transporter cell surface expression.

Speed NK, Matthies HJ, Kennedy JP, Vaughan RA, Javitch JA, Russo SJ, Lindsley CW, Niswender K, Galli A
ACS Chem Neurosci. 2010 1 (7): 476-81

PMID: 22778840 · PMCID: PMC3368666 · DOI:10.1021/cn100031t

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.

MeSH Terms (21)

Allosteric Regulation Animals Cell Membrane Corpus Striatum Dopamine Dopamine Plasma Membrane Transport Proteins Dopaminergic Neurons HEK293 Cells Humans Insulin Isoenzymes Phosphorylation Protein Processing, Post-Translational Protein Transport Proto-Oncogene Proteins c-akt Rats Rats, Sprague-Dawley Recombinant Fusion Proteins Signal Transduction Substrate Specificity Transfection

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