Demonstration of functional coupling between γ-aminobutyric acid (GABA) synthesis and vesicular GABA transport into synaptic vesicles
Demonstration of functional coupling between γ-aminobutyric acid (GABA) synthesis and vesicular GABA transport into synaptic vesicles
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DOI：
10.1073/pnas.0730698100
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发表时间：
2003-04-01
影响因子：
11.1
通讯作者：
Wu, JY
中科院分区：
文献类型：
--
作者：
Jin, H;Wu, H;Wu, JY
L谷氨酸脱羧酶(GAD)在哺乳动物脑中以膜结合形式和可溶性形式存在。在这里，我们提出了膜相关GAD合成GABA和囊泡GABA转运蛋白(VGAT)包装成突触小泡(SVS)之间存在功能和结构上的耦合：这一观点得到了以下观察的支持：首先，用免疫亲和力纯化的GABA能SVS优先从膜结合GAD合成的[H-3]L-谷氨酸合成[H-3]GABA。其次，SV相关的GAD和VGAT的活性似乎是偶联的，因为抑制GAD也会降低VGAT的活性。第三，VGAT和SV相关的钙/钙调蛋白依赖的激酶II与GAD形成蛋白质复合体。还提出了一个模型，将神经元刺激与GABA的增强合成和包装成SVS联系起来。
L-Glutamic acid decarboxylase (GAD) exists as both membrane-associated and soluble forms in the mammalian brain. Here, we propose that there is a functional and structural coupling between the synthesis of gamma-aminobutyric acid (GABA) by membrane-associated GAD and its packaging into synaptic vesicles (SVs) by vesicular GABA transporter (VGAT): This notion is supported by the following observations. First, newly synthesized [H-3]GABA from [H-3]L-glutamate by membrane-associated GAD is taken up preferentially over preexisting GABA by using immunoaffinity-purified GABAergic SVs. Second, the activity of SV-associated GAD and VGAT seems to be coupled because inhibition of GAD also decreases VGAT activity. Third, VGAT and SV-associated Ca2+/ calmodulin-dependent kinase II have been found to form a protein complex with GAD. A model is also proposed to link the neuronal stimulation to enhanced synthesis and packaging of GABA into SVs.