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Structure and function of the dopamine transporter.

N Chen1, M E Reith

  • 1Department of Biomedical and Therapeutic Sciences, College of Medicine, University of Illinois, Box 1649, Peoria, IL 61656, USA.

European Journal of Pharmacology
|October 18, 2000
PubMed
Summary
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The dopamine transporter, crucial for neuron function, has complex binding sites for dopamine and blockers like cocaine. Research suggests distinct structural requirements for its inward and outward transport functions.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • The dopamine transporter (DAT) regulates dopamine uptake into neurons.
  • DAT is a key target for drugs and toxins.
  • Understanding DAT structure and function is vital for neuroscience and pharmacology.

Purpose of the Study:

  • To elucidate the structural basis of dopamine and blocker interactions with the dopamine transporter.
  • To investigate the domains involved in substrate and blocker binding.
  • To explore the transporter's conformational changes and transport modes.

Main Methods:

  • Chimera and site-directed mutagenesis studies.
  • Investigation using sulfhydryl reagents targeting cysteine residues.
  • Analysis of dopamine transporter function in different transport modes.

Related Experiment Videos

Main Results:

  • Evidence suggests multiple amino acid residues contribute to binding domains for dopamine and blockers.
  • Overlapping and separate domains are implicated in substrate and blocker interactions.
  • Conformational changes are important for blocker binding, and distinct structural requirements exist for inward and outward transport.

Conclusions:

  • The dopamine transporter exhibits complex structural features influencing substrate and blocker binding.
  • Distinct structural requirements for inward and outward transport are identified.
  • Developing specific cocaine antagonists targeting the transporter remains a possibility.