N-TERMINUS REGULATION OF VMAT2 MEDIATES METHAMPHETAMINE-STIMULATED EFFLUX

被引：12
作者：
Torres, B. [1 ]
Ruoho, A. E. [1 ]
机构：
[1] Univ Wisconsin, Dept Neurosci, Madison, WI 53706 USA
来源：
NEUROSCIENCE | 2014年 / 259卷
关键词：
vesicular monoamine transporter 2; methamphetamine; kinase; efflux; transporter; monoamine; VESICULAR MONOAMINE TRANSPORTER-2; DOPAMINE TRANSPORTER; MOLECULAR-CLONING; SEQUENCE VARIANTS; AMPHETAMINE; PHOSPHORYLATION; EXPRESSION; RELEASE; GENE; MECHANISM;
D O I：
10.1016/j.neuroscience.2013.11.059
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
The 20 amino acid (AA) N-terminus of the vesicular monoamine transporter 2 (VMAT2) was examined as a regulator of VMAT2 function. Removal of the first 16 or 19 AAs of the N-terminus resulted in a molecule with reduced ability to sequester [H-3]-5HT. A glutathione-S-transferaseconstruct of the N-terminus underwent phosphorylation in the presence of PKC at serines 15 and 18. These putative phosphorylation sites were examined for effects on function. Phospho-mimetic substitution of serines 15 and 18 with aspartate in the full-length VMAT2 resulted in reduced [H-3]-5HT sequestration and reduced methamphetamine (METH)-stimulated efflux of preloaded [H-3]-5HT. In contrast, mutation of serines 15 and 18 to alanines maintained intact net substrate sequestration but eliminated METH-stimulated efflux of pre-accumulated [H-3]-5HT. In summary, these data suggest a model in which the VMAT2 N-terminus regulates monoamine sequestration. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码：194 / 202
页数：9
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