Syntaxin 1A up-regulates GABA transporter expression by subcellular redistribution

Syntaxin 1A up-regulates GABA transporter expression by subcellular redistribution
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Syntaxin 1A 通过亚细胞重新分布上调 GABA 转运蛋白表达

DOI:
10.1080/09687680010029383
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发表时间:
2001
影响因子:
--
通讯作者:
Niambi Horton, Michael W. Quick
Niambi Horton, Michael W. Quick
中科院分区:
生物学4区
文献类型:
--
作者:
Niambi Horton, Michael W. Quick

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神经递质转运体通过各种信号转导机制进行调节,这些机制似乎是为了维持突触间隙中适当的递质水平。其中一种机制是与突触囊泡释放机制相关的转运蛋白的运输。本报告研究了syntaxin 1A对大鼠脑GABA转运体GAT1的运输调节的具体情况,syntaxin 1A是SNARE复合体的质膜成分,参与囊泡膜融合。在海马神经元中,肉毒杆菌神经毒素1C特异性切割syntaxin 1A,通过表面生物素化评估下调质膜GAT1水平,表明syntaxin 1A是GAT1表面表达的积极调节剂。上调与细胞内GAT1水平的降低相关,并在几分钟内完成。这些数据表明syntaxin 1A介导GAT1在一个时间尺度上的重新分配,这对于细胞外GABA水平的快速调节很重要。非洲爪蟾卵母细胞中不同syntaxin 1A结构的表达表明,GAT1的运输需要syntaxin 1A分子的几个部分。这些数据表明GAT1的转运将受到许多已知与syntaxin 1A的各种结构域相互作用的分子的调节控制。
Neurotransmitter transporters are regulated through a variety of signal transduction mechanisms which appear to operate in order to maintain appropriate levels of transmitter in the synaptic cleft. One such mechanism is the trafficking of the transporter in association with synaptic vesicle release machinery. This report examines the specifics of trafficking regulation of the rat brain GABA transporter GAT1 by syntaxin 1A, a plasma membrane component of the SNARE complex which is involved in vesicle membrane fusion. In hippocampal neurons, botulinum neurotoxin 1C, which specifically cleaves syntaxin 1A, down-regulates plasma membrane GAT1 levels as assessed by surface biotinylation, suggesting that syntaxin 1A is a positive regulator of GAT1 surface expression. The up-regulation correlates with a decrease in intracellular GAT1 levels and is complete within several minutes. These data suggest that syntaxin 1A mediates the redistribution of GAT1 on a time scale important for the rapid regulation of extracellular GABA levels. Expression of different syntaxin 1A constructs in Xenopus oocytes suggests that several portions of the syntaxin 1A molecule are required for the trafficking of GAT1. These data suggest that the trafficking of GAT1 will be subject to regulatory control by the many molecules known to interact with various domains of syntaxin 1A.
DOI: 10.1126/science.285.5428.763
发表时间: 1999-07-30
期刊: SCIENCE
影响因子: 56.9
作者:
Ramamoorthy, S;Blakely, RD
通讯作者: Blakely, RD