Study of Molecular Organization of Mouse Cerebellum
小鼠小脑分子组织的研究
基本信息
- 批准号:13308047
- 负责人:
- 金额:$ 29.7万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (A)
- 财政年份:2001
- 资助国家:日本
- 起止时间:2001 至 2003
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
1.By the differential display, microarray, and GeneChip analysis approaches, we explored the gene expression profiles specific to the postnatal developmental stages of mouse cerebellum on a genome-wide basis. In addition, we revealed the spatio-temporal expression patterns of specific genes by RT-PCR and in situ hybridization methods. Integrating all these lines of gene expression information, we have generated the "Cerebellar Development Transcriptome database". By this study, we have succeeded in cloning of many candidates for novel genes responsible for brain development as follows.2.We showed that dendritic clustering and synaptic targeting of Cupidin/Homer, an adaptor protein at postsynaptic density (PSD), coincides those of glutamate receptor-related proteins NR2B and PSD-95 during development of hippocampal neurons, that Cupidin act s as a mobile adaptor in cerebellar granule cells in an activity-dependent manner, and that the Homer family members have differential cellular distributions in developing mouse brains.3.We cloned CAPS2, a paralog of CAPS that regulates Ca2+-dependent exocytosis of secretory granules. CAPS2 was localized to vesicular structures, in which neurotrophins BDNF and NT-3 are included, in parallel fiber terminals of cerebellar granule cells. The overexpression of exogenous CAPS2 in primary cultured granule cells augmented NT-3 release in a depolarization-dependent manner, resulting in promoting survival of Purkinje cells. These data indicate that CAPS2 is a molecule that regulates activity-dependent release of neurotrophins that are indispensable for differentiation and survival of cerebellar neurons.4.We analyzed the structure, function, and brain expression of three genes related to protein phsophorylation (apoptosis activity-related tyrosine kinase AATYK, novel Ser/Thr kinase Ebr, and tyrosine kinase adaptor Cas) and a gene encoded a novel myelin paranodal loop protein.
1.利用差异显示、基因芯片和基因芯片技术,从全基因组水平研究了小鼠小脑发育各阶段的基因表达谱。此外,我们还通过RT-PCR和原位杂交方法揭示了特定基因的时空表达模式。整合所有这些基因表达信息,我们已经产生了“小脑发育转录组数据库”。通过本研究,我们成功地克隆了许多与脑发育相关的新基因候选基因,具体如下:2.我们发现,在海马神经元发育过程中,突触后致密区(postsynaptic density,PSD)的衔接蛋白Cupidin/Homer与谷氨酸受体相关蛋白NR 2B和PSD-95的树突簇集和突触靶向作用是一致的,Cupidin在小脑颗粒细胞中以活性依赖的方式作为移动的适配器,Homer家族成员在发育中的小鼠脑中具有不同的细胞分布。CAPS 2定位于小脑颗粒细胞平行纤维终末的泡状结构,其中包括神经营养因子BDNF和NT-3。在原代培养的颗粒细胞中过表达外源性CAPS 2以去极化依赖的方式增加NT-3的释放,从而促进浦肯野细胞的存活。这些数据表明CAPS 2是一种调节神经营养因子活性依赖性释放的分子,这些神经营养因子对于小脑神经元的分化和存活是必不可少的。4.我们分析了与蛋白磷酸化相关的三个基因的结构、功能和脑表达(凋亡活性相关的酪氨酸激酶AATYK,新的Ser/Thr激酶Ebr,和酪氨酸激酶接头Cas)和编码新的髓磷脂结旁环蛋白的基因。
项目成果
期刊论文数量(51)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
吉川 文生: "遺伝子医学:抗体を利用したタンパクの構造・機能・局在解析"メディカルドゥ. 170 (2003)
Fumio Yoshikawa:“基因医学:使用抗体分析蛋白质结构、功能和定位”Medical Do 170 (2003)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Bosanac, I.: "Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand."Nature. 420. 696-700 (2002)
Bosanac,I.:“肌醇 1,4,5-三磷酸受体结合核心及其配体复合物的结构。”《自然》。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Shiraishi, Y.: "Glutamate-induced declustering of postsynaptic adaptor protein Cupidin (Homer 2/vest-2) in cultured cerebellar granule cells."J.Neurochem.. 87. 364-376 (2003)
Shiraishi, Y.:“培养的小脑颗粒细胞中谷氨酸诱导的突触后接头蛋白 Cupidin (Homer 2/vest-2) 的去聚。”J.Neurochem.. 87. 364-376 (2003)
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Sato, Y.: "Cell specificity and efficiency of the Semliki forest virus vector-and adenovirus vector-mediated gene expression in mouse cerebellum."Journal of Neuroscience Methods. (in press).
Sato, Y.:“Semliki 森林病毒载体和腺病毒载体介导的小鼠小脑基因表达的细胞特异性和效率。”神经科学方法杂志。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Uchida, K.: "Critical regions for activation gating of the inositol 1,4,5-trisphosphate receptor."Journal of Biological Chemistry. 278. 16551-16560 (2003)
Uchida, K.:“肌醇 1,4,5-三磷酸受体激活门控的关键区域。”生物化学杂志。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
FURUICHI Teiichi其他文献
FURUICHI Teiichi的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('FURUICHI Teiichi', 18)}}的其他基金
Study on the molecular mechanisms underlying CAPS-mediated exocytosis of dense-core vesicles containing BDNF and catecholamine
CAPS介导的BDNF和儿茶酚胺致密核囊泡胞吐作用的分子机制研究
- 批准号:
23300137 - 财政年份:2011
- 资助金额:
$ 29.7万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Study of the Structure-Function of IPィイD23ィエD2 Receptor/CaィイD12+ィエD1 Release Channel and IPィイD23ィエD2/CaィイD12+ィエD1 Signaling
IPD23D2受体/CaD12+D1释放通道结构功能及IPD23D2/CaD12+D1信号传导的研究
- 批准号:
10490007 - 财政年份:1998
- 资助金额:
$ 29.7万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Study of the Molecular Structure and Function of IP_3 Receptor/Ca^<2+> Release Channel
IP_3受体/Ca^<2>释放通道的分子结构与功能研究
- 批准号:
08459009 - 财政年份:1996
- 资助金额:
$ 29.7万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Study of the IP_3 receptor family and its diverse roles in various physiological functions
IP_3受体家族及其在多种生理功能中的多种作用的研究
- 批准号:
05455006 - 财政年份:1993
- 资助金额:
$ 29.7万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)
相似海外基金
シナプス形成過程におけるPSD蛋白質Cupidinの機能 -シナプス形態への影響
PSD蛋白Cupidin在突触形成过程中的功能——对突触形态的影响
- 批准号:
12780573 - 财政年份:2000
- 资助金额:
$ 29.7万 - 项目类别:
Grant-in-Aid for Encouragement of Young Scientists (A)