Attenuation of dopamine transporter activity by alpha-synuclein.

Alpha-synuclein accumulates in Lewy bodies in idiopathic Parkinson's disease. Neither the normal function nor contribution of alpha-synuclein to the pathophysiology of neurodegeneration is known. Here we show that a normal function of alpha-synuclein is the negative modulation of human dopamine transporter (hDAT) activity. In cotransfected Ltk(-) cells, alpha-synuclein attenuated the ...
reuptake of dopamine by hDAT, in a manner dependent on expression levels of alpha-synuclein. Alpha-synuclein-mediated inhibition of hDAT activity was independent of expression vectors, cell types and methods of transfection. The alpha-synuclein-mediated decrease in DAT activity occurred through diminished uptake velocity of dopamine, without changes in the affinity of hDAT for dopamine. Co-immunoprecipitation studies confirmed the formation of a stable complex between alpha-synuclein and DAT, through direct protein:protein interactions. Thus, under normal (non-toxic) expression conditions, alpha-synuclein negatively modulates dopamine uptake by DAT.
Mesh Terms:
Animals, Cell Line, Dopamine, Dopamine Plasma Membrane Transport Proteins, Humans, Lewy Bodies, Membrane Glycoproteins, Membrane Transport Proteins, Mice, Nerve Tissue Proteins, Rats, Synucleins, alpha-Synuclein
Neurosci. Lett.
Date: Apr. 17, 2003
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