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Regulation of the Dopamine Transporter by Phosphorylation

  • Chapter
Neurotransmitter Transporters

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 175))

Abstract

The dopamine transporter (DAT) is a neuronal phosphoprotein and target for psychoactive drugs that plays a critical role in terminating dopaminergic transmission by reuptake of dopamine from the synaptic space. Control of DAT activity and plasma membrane expression are therefore central to drug actions and the spatial and temporal regulation of synaptic dopamine levels. DATs rapidly traffic between the plasmamembrane and endosomal compartments in both constitutive and protein kinase C-dependent manners. Kinase activators, phosphatase inhibitors, and transported substrates modulate DAT phosphorylation and activity, but the underlying mechanisms and role of phosphorylation in these processes are poorly understood. Complex adaptive changes in DAT function potentially related to these processes are also induced by psychostimulant and therapeutic transport blockers such as cocaine andmethylphenidate. This chapter provides an overview of the current state of knowledge regarding DAT phosphorylation and its relationship to transporter activity and trafficking. A better understanding of how dopaminergic neurons regulate DAT function and the role of phosphorylation may lead to the identification of novel therapeutic targets for the treatment and prevention of dopaminergic disorders.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, University of North Dakota School of Medicine and Health Sciences, 501 North Columbia Road, Grand Forks, ND, 58203, USA

    J. D. Foster, M. A. Cervinski, B. K. Gorentla & R. A. Vaughan

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  1. J. D. Foster
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  2. M. A. Cervinski
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  3. B. K. Gorentla
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  4. R. A. Vaughan
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  1. Institute of Pharmacology Center for Biomolecular Medicine and Pharmacology, Medical University Vienna, Waehringer Str. 13a, A-1090, Wien, Austria

    Harald H. Sitte  & Michael Freissmuth  & 

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Foster, J.D., Cervinski, M.A., Gorentla, B.K., Vaughan, R.A. (2006). Regulation of the Dopamine Transporter by Phosphorylation. In: Sitte, H.H., Freissmuth, M. (eds) Neurotransmitter Transporters. Handbook of Experimental Pharmacology, vol 175. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-29784-7_10

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