Deciphering mechanisms of synaptic remodeling at the morphological and functional levels

在形态和功能水平上破译突触重塑机制

• 批准号: 17023010
• 负责人: BITO Haruhiko
• 金额: $ 48.83万
• 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 on Priority Areas
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17023010/
• 关键词: 脳・神経; 神経科学; シグナル伝達; 蛋白質; 生理学; CREB; 活動依存性; シナプス; PSD-95; アクチン

Through this program, we identified several new CREB-regulatory kinases. Furthermore, we showed that the immediate early gene Arc is a bona fide CREB target gene, and elucidated the transcriptional mechanisms implicated in activity-dependent Arc gene activation. Additionally, we characterized the essential roles of CaMKI isoforms in the growth of dendrites and axons during the perinatal development of neuronal circuits. Finally, novel modes of regulation of PSD and presynaptic active zone scaffolding proteins (such as PSD-95, RIM1 and Shank) were investigated, with emphasis on their link with actin cytoskeletal remodeling. In parallel, we developed new protocols to visualize and manipulate synapse formation and morphological remodeling of neurons.

通过这个项目，我们发现了几个新的CREB调节蛋白。此外，我们证明了即刻早期基因Arc是一个真正的CREB靶基因，并阐明了与活性依赖的Arc基因激活有关的转录机制。此外，我们还研究了CaMKI异构体在神经回路围生期发育过程中树突和轴突生长过程中的重要作用。最后，我们研究了PSD和突触前活动区支架蛋白(如PSD-95、RIM1和Shank)的调控新模式，重点研究了它们与肌动蛋白细胞骨架重构的关系。与此同时，我们开发了新的方案来可视化和操纵突触形成和神经元的形态重塑。

项目成果

Active zone protein RIM1 functionally associates with presynaptic VDCCs.

活性区蛋白 RIM1 在功能上与突触前 VDCC 相关。

• 发表时间: 2007
• 作者: Sato T;Fukui I;Ohmori H;Kiyonaka S
• 通讯作者: Kiyonaka S

Regulation of osteoclast differentiation and function by the CaMK-CREB pathway

• DOI: 10.1038/nm1515
• 发表时间: 2006-12-01
• 期刊: NATURE MEDICINE
• 影响因子: 82.9
• 作者: Sato, Kojiro;Suematsu, Ayako;Takayanagi, Hiroshi
• 通讯作者: Takayanagi, Hiroshi

Single spine dual FRET imaging to better understanding synaptic biochemical network

单脊柱双 FRET 成像可更好地理解突触生化网络

• 发表时间: 2009
• 作者: Fujii;H ; Inoue;M ; Ishii;Y ; Okuno;H ; Bito;H.
• 通讯作者: H.

Regulation of dendritogenesis via a lipid raft-associated Ca2+/calmodulin-dependent protein kinase CLICK-III/CaMKIγ

通过筏脂质相关 Ca2+/钙调蛋白依赖性蛋白激酶 CLICK-III/CaMKIγ 调节树突发生

• 发表时间: 2007
• 期刊: Neuron 54
• 作者: Takemoto-Kimura S;Ageta-Ishihara N;Nonaka M;Adachi-Morishima A;Mano T;Okamura M;Fujii H;Fuse T;Hoshino M;Suzuki S;M Kojima;Mishina M;Okuno H;Bito H.
• 通讯作者: Bito H.

異なるCaMKK-CaMKI経路による軸索/樹状突起の特異的形成制御

不同 CaMKK-CaMKI 途径对轴突/树突形成的特异性调节

• 发表时间: 2008
• 作者: Takeuchi;T.;Miyazaki T.;Watanabe M.;Mori;H.;Sakimura;K.;Mishina;M.;上田(石原)奈津実
• 通讯作者: 上田(石原)奈津実