Defining the dopamine transporter proteome by convergent biochemical and in silico analyses

Genes, Brain, and Behavior
R MaiyaR D Mayfield

Abstract

Monoamine transporters play a key role in neuronal signaling by mediating reuptake of neurotransmitters from the synapse. The function of the dopamine transporter (DAT), an important member of this family of transporters, is regulated by multiple signaling mechanisms, which result in altered cell surface trafficking of DAT. Protein-protein interactions are likely critical for this mode of transporter regulation. In this study, we identified proteins associated with DAT by immunoprecipitation (IP) followed by mass spectrometry. We identified 20 proteins with diverse cellular functions that can be classified as trafficking proteins, cytoskeletal proteins, ion channels and extracellular matrix-associated proteins. DAT was found to associate with the voltage-gated potassium channel Kv2.1 and synapsin Ib, a protein involved in regulating neurotransmitter release. An in silico analysis provided evidence for common transcriptional regulation of the DAT proteome genes. In summary, this study identified a network of proteins that are primary candidates for functional regulation of the DAT, an important player in mechanisms of mental disorders and drug addiction.

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Citations

Aug 2, 2012·Attention Deficit and Hyperactivity Disorders·Regina TaurinesChristine Freitag
Aug 1, 2013·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Giorgio GoriniR Dayne Mayfield
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Mar 30, 2019·Biochemical and Biophysical Research Communications·Wei YuFederico Sesti
May 15, 2015·Journal of Cell Science·Michela ZaltieriArianna Bellucci

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