Attenuation of dopamine transporter activity by α-synuclein

被引：156

作者：

Wersinger, C ^{[1
]}

Sidhu, A ^{[1
]}

机构：

[1] Georgetown Univ, Dept Pediat, Washington, DC 20007 USA

来源：

NEUROSCIENCE LETTERS | 2003年 / 340卷 / 03期

关键词：

Parkinson's disease; synucleinopathy; neurodegeneration; Lewy bodies; substantia nigra; co-immunoprecipitation striatum;

D O I：

10.1016/S0304-3940(03)00097-1

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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 vas 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, a-synuclein negatively modulates dopamine uptake by DAT. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.

引用

页码：189 / 192

页数：4

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