Molecular mechanism of synatic vesicle exocytosis-Role of vesicle transport in synaptic plasticity

突触小泡胞吐作用的分子机制-小泡运输在突触可塑性中的作用

基本信息

批准号：
10215204
负责人：
SASAKI Takuya
金额：
$ 22.08万
依托单位：
The University of Tokushima Graduate School of Medicine (2000-2001)Osaka University (1998-1999)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2001
项目状态：
已结题

项目摘要

Long-term potentiation (LTP) is believed to provide an important key to understanding the cellular and molecular mechanisms by which memories are formed and stored. Numerous studies strongly suggest that important mechanisms underlying LTP involves alternations in the release of glutamate from the presynaptic cells and the resposiveness of the postsynaptic glutamate receptors. Neurotransmitters including glutamate are released by synaptic vesicle exocytosis which is regulated by many components They are classified into essential and modulatory ones for neurotransmitter release. Rab3A small G protein and Doc2 have been shown to be modulatory components which regulate Ca^<2+>-dependent synaptic vesicle exocytosis. Rab3A cycles between the GDP-bound inactive form and the GTP-bound active form and translocates between the cytosol of the presynaptic nerve terminal and the membranes of synaptic vesicles and the presynaptic plasma membrane. The activation and the translocation are regulated b … More y three regulators (Rab GDIα, Rab3 GAP, Rab3 GEP). Our studies on Rab GDIα-deficient mice indicate that this protein is not essential for basal neurotransmitter release but regulates synaptic plasticity. In contrast, Rab3 GEP-deficient mice show much more severe phenotypes and die immediately after birth due to respiratory insufficiency. We isolated a novel protein that was co-immunoprecipitated with Rab3 GEP and GAP by their respective antibodies from the crude synaptic vesicle fraction of rat brain. The protein, named rabconnectin-3, bound at least both Rab3 GEP and GAP. Doc2 interacts with Munc13 in a diacylglycerol-dependent manner, and this interaction is involved in the docking process. Our studies on Doc2-deficient mice indicate that this protein is not essential for basal neurotransmitter release but regulates synaptic plasticity Further studies on the Rab3A and Doc2 systems are necessary for understanding of the molecular mechanism of synaptic plasticity, which may underlie learning and memory Less

据信长期增强（LTP）为理解形成和存储记忆的细胞和分子机制提供了重要的关键。大量研究强烈表明，LTP潜在的重要机制涉及从突触前细胞释放谷氨酸的替代方法和突触后谷氨酸受体的责任感。包括谷氨酸在内的神经递质通过合成囊泡胞吐释放，该囊泡由许多成分调节，它们被分类为神经递质释放的必需和调节性。 Rab3a小的G蛋白和DOC2已显示为调节CA^<2+> - 依赖性合成蔬菜外胞毒性的调节成分。 RAB3A在GDP结合形式与GTP结合的活性形式之间的循环，并在突触前神经末端的细胞质与突触蔬菜的机制与突触前质膜之间易位。激活和易位受调节b…更多的三个调节剂（RABGDIα，RAB3 GAP，RAB3 GEP）。我们对RABGDIα缺陷小鼠的研究表明，该蛋白对于碱性神经递质释放并不是必需的，而是调节突触可塑性。相比之下，RAB3 GEP缺陷小鼠表现出更严重的表型，并且由于呼吸不足而在出生后立即死亡。我们分离了一种新型蛋白质，该蛋白与Rab3 Gep共免疫沉淀，并通过其各自的抗体从大鼠脑的粗合成场所中的抗体进行了抗体。该蛋白质称为RabConnectin-3，至少绑定了Rab3 GEP和GAP。 DOC2以二酰基甘油依赖性方式与Munc13相互作用，并且这种相互作用与对接过程有关。我们对DOC2缺陷小鼠的研究表明，该蛋白对于碱性神经递质释放并不是必不可少的，但是调节突触可塑性进一步研究RAB3A和DOC2系统对于了解合成可塑性的分子机制是必不可少的，这可能是学习的基础，这可能是学习和记忆的较少的。