These authors contributed equally to this study.
Regulation of dopamine transporter function by protein-protein interactions: new discoveries and methodological challenges
Article first published online: 18 JAN 2010
© 2010 The Authors. Journal Compilation © 2010 International Society for Neurochemistry
Journal of Neurochemistry
Volume 113, Issue 1, pages 27–41, April 2010
How to Cite
Eriksen, J., Jørgensen, T. N. and Gether, U. (2010), Regulation of dopamine transporter function by protein-protein interactions: new discoveries and methodological challenges. Journal of Neurochemistry, 113: 27–41. doi: 10.1111/j.1471-4159.2010.06599.x
- Issue published online: 3 MAR 2010
- Article first published online: 18 JAN 2010
- Received October 16, 2009; revised manuscript received January 6, 2010; accepted January 11, 2010.
- biogenic amines;
- dopaminergic neurons;
- neurotransmitter transporters;
J. Neurochem. (2010) 10.1111/j.1471-4159.2010.06599.x
The dopamine transporter (DAT) plays a key role in regulating dopaminergic signalling in the brain by mediating rapid clearance of dopamine from the synaptic clefts. The psychostimulatory actions of cocaine and amphetamine are primarily the result of a direct interaction of these compounds with DAT leading to attenuated dopamine clearance and for amphetamine even increased dopamine release. In the last decade, intensive efforts have been directed towards understanding the molecular and cellular mechanisms governing the activity and availability of DAT in the plasma membrane of the pre-synaptic neurons. This has led to the identification of a plethora of different kinases, receptors and scaffolding proteins that interact with DAT and hereby either modulate the catalytic activity of the transporter or regulate its trafficking and degradation. Several new tools for studying DAT regulation in live cells have also recently become available such as fluorescently tagged cocaine analogues and fluorescent substrates. Here we review the current knowledge about the role of protein-protein interactions in DAT regulation as well as we describe the most recent methodological developments that have been established to overcome the challenges associated with the study of DAT in endogenous systems.