Regulation of dopamine transporter function by protein-protein interactions: new discoveries and methodological challenges

J Neurochem. 2010 Apr;113(1):27-41. doi: 10.1111/j.1471-4159.2010.06599.x. Epub 2010 Jan 18.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / cytology
  • Dopamine / metabolism*
  • Dopamine Agents / pharmacology
  • Dopamine Plasma Membrane Transport Proteins / chemistry
  • Dopamine Plasma Membrane Transport Proteins / physiology*
  • Electric Conductivity
  • Fluorescent Antibody Technique / methods*
  • Fluorescent Dyes / metabolism*
  • Ion Transport / drug effects
  • Ion Transport / physiology
  • Models, Biological
  • Neurons / drug effects
  • Neurons / metabolism
  • Protein Conformation
  • Protein Processing, Post-Translational* / drug effects
  • Protein Transport / drug effects
  • Protein Transport / physiology
  • Receptors, G-Protein-Coupled / metabolism
  • Ubiquitination / physiology
  • alpha-Synuclein / metabolism


  • Dopamine Agents
  • Dopamine Plasma Membrane Transport Proteins
  • Fluorescent Dyes
  • Receptors, G-Protein-Coupled
  • alpha-Synuclein
  • Dopamine