A CDNA THAT SUPPRESSES MPP+ TOXICITY ENCODES A VESICULAR AMINE TRANSPORTER
A CDNA THAT SUPPRESSES MPP+ TOXICITY ENCODES A VESICULAR AMINE TRANSPORTER
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DOI：
10.1016/0092-8674(92)90425-c
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发表时间：
1992-08-21
期刊：
影响因子：
64.5
通讯作者：
EDWARDS, RH
中科院分区：
文献类型：
--
作者：
LIU, YJ;PETER, D;EDWARDS, RH
经典的神经递质被转运到突触囊泡中，因此它们的释放可以通过神经活动来调节。此外，生物胺的囊泡转运调节对N-甲基-4-苯基吡啶鎓（MPP+）的敏感性，MPP+是产生帕金森病模型的神经毒素N-甲基-1，2，3，6-四氢吡啶的活性代谢物。利用MPP+中的选择，我们使用了基因转移，然后通过质粒拯救来鉴定编码囊泡胺转运蛋白的cDNA克隆。该序列预测了一种新的哺乳动物蛋白，具有12个跨膜结构域，与一类细菌耐药转运蛋白同源。我们只在肾上腺中检测到这种转运蛋白的信使RNA转录本。脑干中的单胺细胞群表达一种独特但高度相关的蛋白质。
Classical neurotransmitters are transported into synaptic vesicles so that their release can be regulated by neural activity. In addition, the vesicular transport of biogenic amines modulates susceptibility to N-methyl-4-phenylpyridinium (MPP+), the active metabolite of the neurotoxin N-methyl-1,2,3,6-tetrahydropyridine that produces a model of Parkinson's disease. Taking advantage of selection in MPP+, we have used gene transfer followed by plasmid rescue to identify a cDNA clone that encodes a vesicular amine transporter. The sequence predicts a novel mammalian protein with 12 transmembrane domains and homology to a class of bacterial drug resistance transporters. We have detected messenger RNA transcripts for this transporter only in the adrenal gland. Monoamine cell populations in the brain stem express a distinct but highly related protein.