The dopamine transporter proteome

• Published in: Journal of neurochemistry Vol. 97; no. s1; pp. 3 - 10
• Main Author: Torres, Gonzalo E.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2006; Blackwell
• Subjects: Animals; Biological and medical sciences; Carrier Proteins - physiology; Cell physiology; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; dopamine; Dopamine - physiology; Dopamine Plasma Membrane Transport Proteins - genetics; Dopamine Plasma Membrane Transport Proteins - physiology; dopamine transporter; Fundamental and applied biological sciences. Psychology; GTP-Binding Proteins - physiology; Humans; Membrane and intracellular transports; Molecular and cellular biology; Nuclear Proteins - physiology; oligomerization; Protein Kinase C - physiology; protein–protein interactions; proteome; Proteome - physiology; Qa-SNARE Proteins - physiology; Synucleins - physiology; trafficking; Vertebrates: nervous system and sense organs; Central nervous system; Homeostasis; Encephalon; Postsynaptic; Attentional disorder; oligomerization; Attention disorder with hyperactivity; trafficking; Presynaptic; Biological receptor; Mood disorder; Drug addiction; Dopamine; Substance abuse; Catecholamine; Uptake; Protein; protein-protein interactions; proteome; Treatment; dopamine transporter; Addiction; Plasma membrane; Neurotransmitter; Mental disorder
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2006.03719.x

Dopamine (DA) uptake through the neuronal plasma membrane DA transporter (DAT) is essential for the maintenance of normal DA homeostasis in the brain. The DAT‐mediated re‐uptake system limits not only the intensity but also the duration of DA actions at presynaptic and postsynaptic receptors. This protein is the primary target for cocaine and amphetamine, both highly addictive and major substances of abuse worldwide. DAT is also the molecular target for therapeutic agents used in the treatment of mental disorders, such as attention deficit hyperactivity disorder and depression. Given the role played by the DAT in regulation of DA neurotransmission and its contribution to the abuse potential of psychostimulants, it becomes not only important but also necessary to understand the functional regulation of this protein. To investigate the cellular and molecular mechanisms associated with DAT function and regulation, our laboratory and others have embarked on a systematic search for DAT protein–protein interactions. Recently, a growing number of proteins have been shown to interact with DAT. These novel interactions might be important in the assembly, targeting, trafficking and/or regulation of transporter function. In this review, I summarize the main findings obtained from the characterization of DAT‐interacting proteins and discuss the functional implications of these novel interactions. Based on these new data, I propose to use the term DAT proteome to explain how interacting proteins regulate DAT function. These novel interactions might help define new mechanisms associated with the function of the transporter.