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Dopamine Transporter Activity Is Modulated by α-Synuclein.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2015 Dec 04; Vol. 290 (49), pp. 29542-54. Date of Electronic Publication: 2015 Oct 06. - Publication Year :
- 2015
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Abstract
- The duration and strength of the dopaminergic signal are regulated by the dopamine transporter (DAT). Drug addiction and neurodegenerative and neuropsychiatric diseases have all been associated with altered DAT activity. The membrane localization and the activity of DAT are regulated by a number of intracellular proteins. α-Synuclein, a protein partner of DAT, is implicated in neurodegenerative disease and drug addiction. Little is known about the regulatory mechanisms of the interaction between DAT and α-synuclein, the cellular location of this interaction, and the functional consequences of this interaction on the basal, amphetamine-induced DAT-mediated dopamine efflux, and membrane microdomain distribution of the transporter. Here, we found that the majority of DAT·α-synuclein protein complexes are found at the plasma membrane of dopaminergic neurons or mammalian cells and that the amphetamine-mediated increase in DAT activity enhances the association of these proteins at the plasma membrane. Further examination of the interaction of DAT and α-synuclein revealed a transient interaction between these two proteins at the plasma membrane. Additionally, we found DAT-induced membrane depolarization enhances plasma membrane localization of α-synuclein, which in turn increases dopamine efflux and enhances DAT localization in cholesterol-rich membrane microdomains.<br /> (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)
- Subjects :
- Amphetamine metabolism
Animals
Biotinylation
Brain metabolism
CHO Cells
Cell Line
Cell Membrane metabolism
Cricetinae
Cricetulus
Dopaminergic Neurons metabolism
Fluorescence Resonance Energy Transfer
Humans
Membrane Microdomains metabolism
Neurodegenerative Diseases metabolism
Synaptic Transmission
Synucleins metabolism
Dopamine metabolism
Dopamine Plasma Membrane Transport Proteins metabolism
alpha-Synuclein metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 290
- Issue :
- 49
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 26442590
- Full Text :
- https://doi.org/10.1074/jbc.M115.691592