Role of the Rab family small G proteins in synaptic plasticity

Rab 家族小 G 蛋白在突触可塑性中的作用

• 批准号: 13470025
• 负责人: SASAKI Takuya
• 金额: $ 9.28万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470025/
• 关键词: synaptic plasticity; vesicle transport; Rab3A; regulators; Rab3 GEP; Rab3 GAP; Rab GDI; Rabconnectin-3; 神経伝達物質; グルタミン酸受容体; 神経伝達物質放出; Rab3 GEP

Long-term potentiation (LTP) is believed to provide an important key to understanding the cellular and molecular mechanisms by winch 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 responsiveness 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 has been shown to be a modulatory component which regulates Ca^<2+>-dependent synaptic vesicle exocytosis. Rab3A cycles between the GDP-bound inactive form (GDP-Rab3A) and the GTP-bound active form (GTP-Rab3A) 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 translocati … More on are regulated by three regulators (Rab GDI, Rab3 GAP, Rab3 GEP). Our previous studies on Rab GDIα-deficient mice had revealed that Rab GDIα is not essential for basal neurotransmitter release but suppress hyperexcitability via modulation of synaptic plasticity. In tins study, we found that Rab3 GEP-deficient mice show much more severe phenotypes and die immediately after birth due to respiratory insufficiency. Electron microscopic analysis of the neuromuscular junction revealed that total numbers of synaptic vesicles and active zones are markedly reduced. 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. This protein, named rabconnectin-3, bound at least both Rab3 GEP and GAP. Tissue and subcellular distribution analyses in rat indicated that rabcoithectin-3 was abundantly expressed in the brain where it was enriched in the synaptic vesicle fraction. Immunofluorescence and immunoelectron microscopy revealed that rabconnectin-3 was concentrated on synaptic vesicles at synapses. Less

长期增强（LTP）是理解细胞和分子储存的重要关键，其中重要的研究涉及ltp释放谷氨酸的替代纳特囊泡外胞菌的释放，许多成分都定期地分类为基本和模块化。 Rab3a）和GTP结合形式（GTP-RAB3A），并在突触前神经末端的胞质和突触囊泡质膜的膜之间易位。 GEP）。尊敬的是，突触囊泡的总数显着降低，并由该蛋白的粗囊囊泡分离出来。突触囊泡的分数

项目成果

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Orita，S.：“Doc2α 作为 Ca ^ 2+ 依赖性胞吐作用的调节剂”Methods Enzymol.. 329. 83-90 (2001)

Nagano, F.: "Rabconnectin-3 : A novel protein that binds GDP/GTP exchange protein and GTPase-activating protein for Rab3 small G protein family"J. Biol. Chem.. 277. 9629-9632 (2002)

Nagano, F.：“Rabconnectin-3：一种结合 GDP/GTP 交换蛋白和 Rab3 小 G 蛋白家族的 GTP 酶激活蛋白的新型蛋白”J.

Tanaka, M., et al.: "Role of Rab3 GDP/GTP exchange protein in synaptic vesicle trafficking at the mouse neuromuscular junction."Mol. Biol. Cell. 12. 1421-1430 (2001)

Tanaka, M. 等人：“Rab3 GDP/GTP 交换蛋白在小鼠神经肌肉接头突触小泡运输中的作用。”

Tanaka, M.: "Role of Rab3 GDP/GTP exchange protein in synaptic vesicle trafficking at the mouse neuromuscular junction"Mol. Biol. Cell. 12. 1421-1430 (2001)

Tanaka, M.：“Rab3 GDP/GTP 交换蛋白在小鼠神经肌肉接头突触小泡运输中的作用”Mol。