Neuronal development via redox signaling and mitochondrial dynamics
通过氧化还原信号和线粒体动力学的神经元发育
基本信息
- 批准号:20300133
- 负责人:
- 金额:$ 12.56万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B)
- 财政年份:2008
- 资助国家:日本
- 起止时间:2008 至 2010
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Neuronal network and axonal guidance are critical processes that are highly regulated through extracellular signaling. Neuronal outgrowth is directed by repelling signaling molecules such as semaphorins. Redox reaction via activation of oxidoreductase MICAL has been shown to be involved in semaphorin-mediated signaling, however, the molecular basis was unknown. We have previously identified a novel GTPase named CRAG which was activated by reactive oxygen species generated by semaphorin and translocated to the nucleus. In this study, we found that CRAG mediated neuronal cell survival pathway by transcriptional regulation of AP-1 and SRF in the nucleus. In addition, CRAG was found to activate anti-oxidant signaling which alsocontributes to the cell survival. Furthermore, we succeeded to generate CRAG conditionalknockout mice. These mice will provide an important information to understand the physiological role of CARG during neuronal development. On the other hand, MITOL is a novel mitochondrialubiquitin ligase which regulates mitochondrial dynamics by ubiquitination of mitochondrial fission factor Drp1. Subsequently, we suggested that MITOL is involved in mitochondrial quality control by ubiquitination of unfolded proteins such as mutant SOD1 and expanded polyQ accumulated in mitochondria. However, the exact role of MITOL is still obscure. Most recently we identified two physiological substrates of MITOL, MAP1B-LC1 and mitofusin2. Further analysis of MITOL will uncover the new role of mitochondria, thereby contributing to a greater understanding of the molecular basis of the neurodegenerative disorders.
神经元网络和轴突引导是通过细胞外信号高度调节的关键过程。神经元出生是通过排斥信号分子(例如信号素)指导的。通过激活氧化还原酶微方的氧化还原反应已被证明参与了信号蛋白介导的信号传导,但是,分子基础尚不清楚。我们先前已经鉴定出一种名为CRAG的新型GTPase,该GTPase由Semaphorin产生并转移到细胞核中的活性氧激活。在这项研究中,我们发现CRAG通过核中AP-1和SRF的转录调节介导的神经元细胞存活途径。此外,发现CRAG激活了抗氧化信号,该信号转导向细胞存活。此外,我们成功地生成了crag procentionallocknockout小鼠。这些小鼠将提供重要的信息,以了解CARG在神经元发育中的生理作用。另一方面,有线粒体是一种新型的线粒体蛋白酶连接酶,通过泛素化线粒体裂变因子DRP1来调节线粒体动力学。随后,我们建议通过泛素化未折叠的蛋白(例如突变SOD1)和在线粒体中积累的PolyQ扩展来参与线粒体质量控制。但是,有丝醇的确切作用仍然是晦涩的。最近,我们确定了两个生理底物MAP1B-LC1和MITOFUSIN2。进一步分析有线粒体将揭示线粒体的新作用,从而有助于更了解神经退行性疾病的分子基础。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
A mitochondrial ubiquitin ligase MITOL controls cell toxicity of polyglutamine-expanded protein
- DOI:10.1016/j.mito.2010.09.001
- 发表时间:2011-01-01
- 期刊:
- 影响因子:4.4
- 作者:Sugiura, Ayumu;Yonashiro, Ryo;Yanagi, Shigeru
- 通讯作者:Yanagi, Shigeru
A role of MITOL in the regulation of ER-mitochondriajunction via Mfn2
MITOL 通过 Mfn2 调节 ER 线粒体连接的作用
- DOI:
- 发表时间:2010
- 期刊:
- 影响因子:0
- 作者:Sugiura;A.
- 通讯作者:A.
A role of MITOL in the regulation of ER-mitochondria junction via Mfn2.
MITOL 通过 Mfn2 调节 ER-线粒体连接的作用。
- DOI:
- 发表时间:2010
- 期刊:
- 影响因子:0
- 作者:Sugiura A.;Watanabe K.;Inatome R.;Yanagi;S
- 通讯作者:S
MITOLによるMfn2の制御機構の解析Analysis of regulatory mechanism of Mfn2 by MITOL.
MITOL对Mfn2的调控机制分析。
- DOI:
- 发表时间:2010
- 期刊:
- 影响因子:0
- 作者:渡辺香林;杉浦歩;柳茂
- 通讯作者:柳茂
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YANAGI Shigeru其他文献
YANAGI Shigeru的其他文献
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{{ truncateString('YANAGI Shigeru', 18)}}的其他基金
Role of MITOL in Alzheimer's disease
MITOL 在阿尔茨海默病中的作用
- 批准号:
16K15224 - 财政年份:2016
- 资助金额:
$ 12.56万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Role of MITOL in mitochondrial dynamics
MITOL 在线粒体动力学中的作用
- 批准号:
26293072 - 财政年份:2014
- 资助金额:
$ 12.56万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Development of CRAG gene therapy for neurodegenerative diseases
神经退行性疾病CRAG基因疗法的开发
- 批准号:
25640040 - 财政年份:2013
- 资助金额:
$ 12.56万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Role of MITOL in mitochondrial function and oxidative stress signaling
MITOL 在线粒体功能和氧化应激信号传导中的作用
- 批准号:
23650195 - 财政年份:2011
- 资助金额:
$ 12.56万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Elucidation of molecular signaling mechanism of axonal guidance
阐明轴突引导的分子信号机制
- 批准号:
17300117 - 财政年份:2005
- 资助金额:
$ 12.56万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Elucidation of molecular signaling mechanism of axonal guidance
阐明轴突引导的分子信号机制
- 批准号:
15590247 - 财政年份:2003
- 资助金额:
$ 12.56万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Action of novel non-receptor type protein-tyrosine kinase, p72^<syk>in immune cells.
新型非受体型蛋白酪氨酸激酶 p72^<syk> 在免疫细胞中的作用。
- 批准号:
05670117 - 财政年份:1993
- 资助金额:
$ 12.56万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)
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