| Literature DB >> 26147533 |
Shuyong Zhu1, Chengjiang Zhao2, Yingying Wu2, Qiaoqiao Yang3, Aiyun Shao1, Tiepeng Wang1, Jianfu Wu1, Yanqing Yin1, Yandong Li1, Jincan Hou1, Xinhua Zhang4, Guomin Zhou5, Xiaosong Gu6, Xiaomin Wang7, Xosé R Bustelo8, Jiawei Zhou1.
Abstract
Dopamine (DA) homeostasis is essential for a variety of brain activities. Dopamine transporter (DAT)-mediated DA reuptake is one of the most critical mechanisms for normal DA homeostasis. However, the molecular mechanisms underlying the regulation of DAT activity in the brain remain poorly understood. Here we show that the Rho-family guanine nucleotide exchange factor protein Vav2 is required for DAT cell surface expression and transporter activity modulated by glial cell line-derived neurotrophic factor (GDNF) and its cognate receptor Ret. Mice deficient in either Vav2 or Ret displayed elevated DAT activity, which was accompanied by an increase in intracellular DA selectively in the nucleus accumbens. Vav2(-/-) mice exposed to cocaine showed reduced DAT activity and diminished behavioral cocaine response. Our data demonstrate that Vav2 is a determinant of DAT trafficking in vivo and contributes to the maintenance of DA homeostasis in limbic DA neuron terminals.Entities:
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Year: 2015 PMID： 26147533 DOI： 10.1038/nn.4060
Source DB: PubMed Journal: Nat Neurosci ISSN： 1097-6256 Impact factor: 24.884