RRC ID 34564
Author Zhu S, Zhao C, Wu Y, Yang Q, Shao A, Wang T, Wu J, Yin Y, Li Y, Hou J, Zhang X, Zhou G, Gu X, Wang X, Bustelo XR, Zhou J.
Title Identification of a Vav2-dependent mechanism for GDNF/Ret control of mesolimbic DAT trafficking.
Journal Nat Neurosci
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.
Volume 18(8)
Pages 1084-93
Published 2015-8-1
DOI 10.1038/nn.4060
PII nn.4060
PMID 26147533
MeSH Animals Behavior, Animal / drug effects Cocaine / pharmacology Dopamine / metabolism* Dopamine Plasma Membrane Transport Proteins / metabolism* Dopaminergic Neurons / metabolism* Glial Cell Line-Derived Neurotrophic Factor / metabolism* Homeostasis Limbic System / metabolism* Male Mice Mice, Inbred C57BL Mice, Knockout Nucleus Accumbens / metabolism* Protein Transport Proto-Oncogene Proteins c-ret / metabolism* Proto-Oncogene Proteins c-vav Signal Transduction / physiology*
IF 20.071
Times Cited 20
Mice RBRC02095