title: A Physical Interaction between the Dopamine Transporter and DJ-1 Facilitates Increased Dopamine Reuptake.
abstract: The regulation of the dopamine transporter (DAT) impacts extracellular dopamine levels after release from dopaminergic neurons. Furthermore, a variety of protein partners have been identified that can interact with and modulate DAT function. In this study we show that DJ-1 can potentially modulate DAT function. Co-expression of DAT and DJ-1 in HEK-293T cells leads to an increase in [3H] dopamine uptake that does not appear to be mediated by increased total DAT expression but rather through an increase in DAT cell surface localization. In addition, through a series of GST affinity purifications and co-immunoprecipitations, we provide evidence that the DAT can be found in a complex with DJ-1, which involve distinct regions within both DAT and DJ-1. Using in vitro binding experiments we also show that this complex can be formed in part by a direct interaction between DAT and DJ-1. Co-expression of a mini-gene that can disrupt the DAT/DJ-1 complex appears to block the increase in [3H] dopamine uptake by DJ-1. Mutations in DJ-1 have been linked to familial forms of Parkinson's disease, yet the normal physiological function of DJ-1 remains unclear. Our study suggests that DJ-1 may also play a role in regulating dopamine levels by modifying DAT activity.
authors: Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada.
authors: Beryl
authors: B
authors: Luk
authors: Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.
authors: Mohinuddin
authors: M
authors: Mohammed
authors: Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.
authors: Fang
authors: F
authors: Liu
authors: Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada.
authors: Frank J S
authors: FJ
authors: Lee
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D004298:Dopamine / Q000235:genetics / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D000071617:Protein Deglycase DJ-1
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D004298:Dopamine