Synucleins Antagonize Endoplasmic Reticulum Function to Modulate Dopamine Transporter Trafficking

Adam W. Oaks, Nicholas Marsh-Armstrong, Jessica M. Jones, Joel J. Credle, Anita Sidhu

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Synaptic re-uptake of dopamine is dependent on the dopamine transporter (DAT), which is regulated by its distribution to the cell surface. DAT trafficking is modulated by the Parkinson's disease-linked protein alpha-synuclein, but the contribution of synuclein family members beta-synuclein and gamma-synuclein to DAT trafficking is not known. Here we use SH-SY5Y cells as a model of DAT trafficking to demonstrate that all three synucleins negatively regulate cell surface distribution of DAT. Under these conditions the synucleins limit export of DAT from the endoplasmic reticulum (ER) by impairment of the ER-Golgi transition, leading to accumulation of DAT in this compartment. This mechanism for regulating DAT export indirectly through effects on ER and Golgi function represents a previously unappreciated role for the extended synuclein family that is likely applicable to trafficking of the many proteins that rely on the secretory pathway.

Original languageEnglish (US)
Article numbere70872
JournalPLoS One
Volume8
Issue number8
DOIs
StatePublished - Aug 13 2013
Externally publishedYes

Fingerprint

Synucleins
Dopamine Plasma Membrane Transport Proteins
dopamine
Endoplasmic Reticulum
endoplasmic reticulum
transporters
gamma-Synuclein
beta-Synuclein
extended families
alpha-Synuclein
Secretory Pathway
Protein Transport
Parkinson disease
cells
Parkinson Disease
Dopamine
Proteins
proteins

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Synucleins Antagonize Endoplasmic Reticulum Function to Modulate Dopamine Transporter Trafficking. / Oaks, Adam W.; Marsh-Armstrong, Nicholas; Jones, Jessica M.; Credle, Joel J.; Sidhu, Anita.

In: PLoS One, Vol. 8, No. 8, e70872, 13.08.2013.

Research output: Contribution to journalArticle

Oaks, Adam W. ; Marsh-Armstrong, Nicholas ; Jones, Jessica M. ; Credle, Joel J. ; Sidhu, Anita. / Synucleins Antagonize Endoplasmic Reticulum Function to Modulate Dopamine Transporter Trafficking. In: PLoS One. 2013 ; Vol. 8, No. 8.
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