Synucleins antagonize endoplasmic reticulum function to modulate dopamine transporter trafficking

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...

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Published in:PloS one 2013-08, Vol.8 (8), p.e70872-e70872
Main Authors: Oaks, Adam W, Marsh-Armstrong, Nicholas, Jones, Jessica M, Credle, Joel J, Sidhu, Anita
Format: Article
Language:English
Subjects:
Analysis
Biochemistry
Biology
Brain - metabolism
Cell Line
Cell Membrane - metabolism
Cell surface
Cellular biology
Dopamine
Dopamine Plasma Membrane Transport Proteins - genetics
Dopamine Plasma Membrane Transport Proteins - metabolism
Dopamine transporter
Endoplasmic reticulum
Endoplasmic Reticulum - metabolism
Exports
Gene Expression
Golgi apparatus
Golgi Apparatus - metabolism
Humans
Laboratories
Movement disorders
Neurochemistry
Neurodegenerative diseases
Neurosciences
Parkinson's disease
Phenols (Class of compounds)
Protein Binding
Protein Transport
Proteins
Recovery (Medical)
Rodents
Synuclein
Synucleins - metabolism
Transfection
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cited_by cdi_FETCH-LOGICAL-c692t-1d3d88bb2ea65c36dd849a2dddacb46347ab32b7e99eaba49bd5750cc71e0f2e3
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Sidhu, Anita
description 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.
doi_str_mv 10.1371/journal.pone.0070872
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subjects Analysis
Biochemistry
Biology
Brain - metabolism
Cell Line
Cell Membrane - metabolism
Cell surface
Cellular biology
Dopamine
Dopamine Plasma Membrane Transport Proteins - genetics
Dopamine Plasma Membrane Transport Proteins - metabolism
Dopamine transporter
Endoplasmic reticulum
Endoplasmic Reticulum - metabolism
Exports
Gene Expression
Golgi apparatus
Golgi Apparatus - metabolism
Humans
Laboratories
Movement disorders
Neurochemistry
Neurodegenerative diseases
Neurosciences
Parkinson's disease
Phenols (Class of compounds)
Protein Binding
Protein Transport
Proteins
Recovery (Medical)
Rodents
Synuclein
Synucleins - metabolism
Transfection
title Synucleins antagonize endoplasmic reticulum function to modulate dopamine transporter trafficking
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