Transport of Neurotransmitter Into Synaptic Vesicles
将神经递质转运到突触小泡中
基本信息
- 批准号:6653183
- 负责人:
- 金额:$ 24.96万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1993
- 资助国家:美国
- 起止时间:1993-07-01 至 2006-08-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Synaptic transmission depends on the transport of classical neurotransmitters from the cytoplasm, where they are synthesized and accumulate after reuptake from the extracellular space, into synaptic vesicles, which then undergo regulated exocytosis. To understand how transport into synaptic vesicles contributes to neurotransmitter release, the postsynaptic response and ultimately behavior, we have focused on the proteins responsible for this basic function of the nerve terminal. In previous work, we have identified two families of proteins responsible for the transport of cationic and neutral transmitters into synaptic vesicles. However, the proteins responsible for vesicular glutamate transport have proven elusive. We have recently found that a protein previously suggested to mediate the Na+-dependent uptake of inorganic phosphate across the plasma membrane, in fact transports glutamate into synaptic vesicles. In addition to H+-driven glutamate transport, the protein (VGLUT1) exhibits an unusual chloride conductance inhibited by glutamate. To assess its channel-like properties and its transport function, we will characterize the interactions of VGLUT1 with chloride and protons. We will also assess the potential for VGLUT1 to transport glutamate (and phosphate) at the plasma membrane. Since the regulation of VGLUT1 may influence synaptic vesicle filling and VGLUT1 contains two polyproline domains, we will further characterize its interaction with other proteins. The expression of VGLUT1 by only a subset of glutamate neurons also suggests the existence of another isoform, and recent work describes a closely related putative phosphate transporter. We will thus examine the distribution of this protein and study its transport function. To assess the role of VGLUT1 in vivo, we will disrupt the gene in mice and examine the physiological effects. These experiments will help to understand the transport of glutamate at the nerve terminal and its role in transmitter release, synaptic plasticity, excitotoxicity and behavior.
突触传递依赖于经典神经递质从细胞质的运输,它们在细胞质中合成并从细胞外空间重新摄取后积累到突触囊泡中,然后经过调节的胞外分泌。为了了解转运到突触囊泡如何促进神经递质释放、突触后反应和最终行为,我们将重点放在负责神经末梢这一基本功能的蛋白质上。在之前的工作中,我们已经确定了两个负责将阳离子和中性递质转运到突触囊泡中的蛋白家族。然而,负责谷氨酸囊泡运输的蛋白质已被证明是难以捉摸的。我们最近发现,一种先前被认为介导Na+依赖性无机磷酸盐通过质膜摄取的蛋白质,实际上将谷氨酸转运到突触囊泡中。除了H+驱动的谷氨酸运输外,该蛋白(VGLUT1)还表现出受谷氨酸抑制的不寻常的氯离子传导。为了评估其通道性质及其传输功能,我们将表征VGLUT1与氯化物和质子的相互作用。我们还将评估VGLUT1在质膜上转运谷氨酸(和磷酸盐)的潜力。由于VGLUT1的调控可能影响突触囊泡填充,并且VGLUT1含有两个聚脯氨酸结构域,我们将进一步表征其与其他蛋白质的相互作用。VGLUT1仅在谷氨酸神经元的一个子集中表达,也表明存在另一种异构体,最近的研究描述了一种密切相关的推定磷酸盐转运体。因此,我们将检查这种蛋白质的分布并研究其运输功能。为了评估VGLUT1在体内的作用,我们将在小鼠中破坏该基因并检测其生理效应。这些实验将有助于了解谷氨酸在神经末梢的转运及其在递质释放、突触可塑性、兴奋毒性和行为中的作用。
项目成果
期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
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ROBERT H EDWARDS其他文献
ROBERT H EDWARDS的其他文献
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{{ truncateString('ROBERT H EDWARDS', 18)}}的其他基金
Structural Basis of Vesicular Neurotransmitter Transport
囊泡神经递质运输的结构基础
- 批准号:
9258506 - 财政年份:2015
- 资助金额:
$ 24.96万 - 项目类别:
Structural Basis of Vesicular Neurotransmitter Transport
囊泡神经递质运输的结构基础
- 批准号:
9920217 - 财政年份:2015
- 资助金额:
$ 24.96万 - 项目类别:
Structural Basis of Vesicular Neurotransmitter Transport
囊泡神经递质运输的结构基础
- 批准号:
8964141 - 财政年份:2015
- 资助金额:
$ 24.96万 - 项目类别:
Structural Basis of Vesicular Neurotransmitter Transport
囊泡神经递质运输的结构基础
- 批准号:
10614384 - 财政年份:2015
- 资助金额:
$ 24.96万 - 项目类别:
Structural Basis of Vesicular Neurotransmitter Transport
囊泡神经递质运输的结构基础
- 批准号:
10392888 - 财政年份:2015
- 资助金额:
$ 24.96万 - 项目类别:
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