title: Palmitoylation mechanisms in dopamine transporter regulation.
abstract: The neurotransmitter dopamine (DA) plays a key role in several biological processes including reward, mood, motor activity and attention. Synaptic DA homeostasis is controlled by the dopamine transporter (DAT) which transports extracellular DA into the presynaptic neuron after release and regulates its availability to receptors. Many neurological disorders such as schizophrenia, bipolar disorder, Parkinson disease and attention-deficit hyperactivity disorder are associated with imbalances in DA homeostasis that may be related to DAT dysfunction. DAT is also a target of psychostimulant and therapeutic drugs that inhibit DA reuptake and lead to elevated dopaminergic neurotransmission. We have recently demonstrated the acute and chronic modulation of DA reuptake activity and DAT stability through S-palmitoylation, the linkage of a 16-carbon palmitate group to cysteine via a thioester bond. This review summarizes the properties and regulation of DAT palmitoylation and describes how it serves to affect various transporter functions. Better understanding of the role of palmitoylation in regulation of DAT function may lead to identification of therapeutic targets for modulation of DA homeostasis in the treatment of dopaminergic disorders.
authors.affiliation: Department of Biomedical Sciences, University of North Dakota, School of Medicine and Health Sciences, Grand Forks, ND 58202, United States.
authors.forename: Danielle E
authors.initials: DE
authors.lastname: Rastedt
authors.affiliation: Department of Biomedical Sciences, University of North Dakota, School of Medicine and Health Sciences, Grand Forks, ND 58202, United States.
authors.forename: Roxanne A
authors.initials: RA
authors.lastname: Vaughan
authors.affiliation: Department of Biomedical Sciences, University of North Dakota, School of Medicine and Health Sciences, Grand Forks, ND 58202, United States. Electronic address: james.d.foster@med.und.edu.
authors.forename: James D
authors.initials: JD
authors.lastname: Foster
mesh_terms: D000818:Animals; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D006801:Humans; D054878:Lipoylation / Q000502:physiology*; D011499:Protein Processing, Post-Translational / Q000502:physiology
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins
keywords: 2 Bromopalmitate; Acyl protein thioesterase; Palmitoyl acyl transferase; Phosphorylation; Posttranslational modification; Protein trafficking