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Substrates dissociate dopamine transporter oligomers.

Nianhang Chen1, Maarten E A Reith

  • 1Department of Psychiatry, Millhauser Laboratories, New York University School of Medicine, New York 10016, USA.

Journal of Neurochemistry
|December 20, 2007
PubMed
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Substrates like dopamine and amphetamine regulate dopamine transporter (DAT) oligomerization and cell surface presence. Inhibiting endocytosis prevents these substrate-induced changes, linking DAT oligomerization to cell surface regulation.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Substrate-induced endocytic trafficking of the dopamine transporter (DAT) is known.
  • Regulation of DAT oligomerization by substrates remains poorly understood.

Purpose of the Study:

  • Investigate substrate effects on DAT oligomerization.
  • Explore the link between DAT oligomerization and cell surface expression.

Main Methods:

  • Used N-terminal tagged DAT constructs in HEK cells.
  • Assessed DAT oligomerization via co-immunoprecipitation and cross-linking (copper sulfate phenanthroline).
  • Measured surface DAT levels using biotinylation and inhibited endocytosis (phenylarsine oxide, sucrose).

Main Results:

Related Experiment Videos

  • Dopamine and amphetamine reduced DAT oligomerization and surface expression.
  • Endocytosis inhibition counteracted substrate-induced reductions in DAT cross-linking.
  • Results suggest substrate regulation of DAT oligomerization.

Conclusions:

  • This study is the first to show substrate regulation of dopamine transporter (DAT) oligomerization.
  • A potential link exists between DAT oligomerization and endocytic mechanisms affecting surface DAT levels.