Cellular dynamics of functional molecules and second messengers during synaptic transmission

突触传递过程中功能分子和第二信使的细胞动力学

• 批准号: 07508004
• 负责人: MIKOSHIBA Katsuhiko
• 金额: $ 13.82万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07508004/
• 关键词: neurotransmitter; neurotransmission; synaptotagmin; inositol polyphosphate; synapse; sinaptic vesicle; IP_3; IP_3レセプター; カルシウムイオン; 情報伝達; カルシウムチャネル; 小胞体; セカンドメッセンジャー

The inositol high-polyphodphate series (IP4, IP5 and IP6 ; IHPS) inhibit the neurotransmission through binding to the 2nd C2 domain of synaptotagmin (Syt), synaptic vesicle membrane proteins using superior cervical ganglion and squid giant synapse. Now we have revealed several proteins, including alpha adaptins which are specific subunits of clathrin AP2, from mouse brain were eluted by affinity elution chromatography from the C2 domain of Syt II-immobilized Sepharose using 50muM of inositol hexakisphosphate (IP6). The interaction between Syt II and AP2 was inhibited more strongly by IHPS than by the same concentration of IP3. Limited digestion of mouse crude synaptosomal fractions with trypsin revealed different cleavage pattern between in the presenc and the absence of 50muM IP6. These results suggests that IHPS-binding to C2B domain of synaptotagmin alter the state of protein-protein interaction such as synaptotagmin-AP2 interaction, which may induce the inhibition of some events involved in the neurotransmission, e.g. endocytosis.

肌醇高聚磷酸酯系列（IP4、IP5和IP6；IHPS）通过与突触结合蛋白（Syt）的第二个C2结构域结合来抑制神经传递，突触结合蛋白是利用颈上神经节和鱿鱼巨突触的突触小泡膜蛋白。现在我们已经揭示了小鼠大脑中的几种蛋白质，包括网格蛋白 AP2 的特定亚基 α 适应素，使用 50μM 六磷酸肌醇 (IP6)，通过亲和洗脱色谱从 Syt II 固定琼脂糖凝胶的 C2 结构域中洗脱。 IHPS 对 Syt II 和 AP2 之间相互作用的抑制作用比相同浓度的 IP3 更强。用胰蛋白酶对小鼠粗制突触体级分进行有限消化，揭示了存在和不存在 50μM IP6 时的不同裂解模式。这些结果表明，IHPS 与突触结合蛋白 C2B 结构域的结合改变了蛋白质-蛋白质相互作用的状态，例如突触结合蛋白-AP2 相互作用，这可能会诱导神经传递中涉及的一些事件的抑制，例如神经传递。内吞作用。

项目成果

Matsumoto, Mineo: "Ataxia and epileptic seizures in mice lacking type 1 inositol 1,4,5-trisphoshate receptor." Nature. 379. 168-171 (1996)

Matsumoto, Mineo：“缺乏 1 型肌醇 1,4,5-三磷酸受体的小鼠会出现共济失调和癫痫发作。”

Inoue, Yoshiro: "Cell death of oligodendrocytes or demyelination induced by overexpression of proteolipid protein depending on expressed gene dosage." Neuroscience Research. 25. 161-172 (1996)

Inoue, Yoshiro：“蛋白脂质蛋白过度表达诱导少突胶质细胞死亡或脱髓鞘，具体取决于表达基因的剂量。”

Miyawaki, A. et al.: "Proceedings of the Yamada Conference XXXIX on Calcium as Cell Signal April 26-28, 1994 Tokyo, Japan (PP154-164)" IGAKU-SHOIN, 293 (1995)

Miyawaki, A. 等人：“关于钙作为细胞信号的山田会议 XXXIX 的会议记录，1994 年 4 月 26-28 日，日本东京 (PP154-164)” IGAKU-SHOIN, 293 (1995)

Inoue, Yoshiro et al.: "Cell death of oligodendrocytes or demyelination induced by overexpression of proteolipid protein depending on expressed gene dosage." Neuroscience Research. 25. 161-172 (1996)

Inoue、Yoshiro 等人：“蛋白脂质蛋白过度表达诱导少突胶质细胞死亡或脱髓鞘，具体取决于表达基因的剂量。”

Hirota, J. et al.: "Genes for development, cell growth and infectious diseases (A dacade of Pasteur Riken collaboration)(PP81-96)" John Libbey EUROTEXT, 262 (1995)

Hirota, J. 等人：“发育、细胞生长和传染病的基因（巴斯德理研合作的十年）(PP81-96)” John Libbey EUROTEXT, 262 (1995)