Phosphorylation mechanisms in dopamine transporter regulation.
The dopamine transporter (DAT) is a plasma membrane phosphoprotein that actively translocates extracellular dopamine (DA) into presynaptic neurons. The transporter is the primary mechanism for control of DA levels and subsequent neurotransmission, and is the target for abused and therapeutic drugs that exert their effects by suppressing reuptake. The transport capacity of DAT is acutely regulated by signaling systems and drug exposure, providing neurons the ability to fine-tune DA clearance in response to specific conditions. Kinase pathways play major roles in these mechanisms, and this review summarizes the current status of DAT phosphorylation characteristics and the evidence linking transporter phosphorylation to control of reuptake and other functions. Greater understanding of these processes may aid in elucidation of their possible contributions to DA disease states and suggest specific phosphorylation sites as targets for therapeutic manipulation of reuptake.
Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks ND 58202 United States.
James D
JD
Foster
Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks ND 58202 United States. Electronic address: roxanne.vaughan@med.und.edu.
Roxanne A
RA
Vaughan
D000818:Animals; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation / Q000502:physiology*; D011499:Protein Processing, Post-Translational / Q000502:physiology
D050483:Dopamine Plasma Membrane Transport Proteins
Amphetamine; Extracellular signal regulated kinase; PIN1; Phospho-specific antibody; Protein kinase C; Protein phosphatase 1/2A