Elucidation of APC2 functions in the regulation of cytoskeletal dynamics during neuronal development

阐明 APC2 在神经元发育过程中细胞骨架动力学调节中的功能

• 批准号: 23300126
• 负责人: SHINTANI Takafumi
• 金额: $ 12.23万
• 依托单位: National Institute for Basic Biology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23300126/
• 关键词: 神経発生; 神経分化; 細胞骨格; 細胞移動; 神経回路; 神経軸索; 記憶・学習; 情報伝達; 神経組織; 神経回路形成

Adenomatous polyposis coli 2 (APC2) is mainly expressed in the nervous system and known to regulate microtubule stability in neurons. I show that a lack of Apc2 induces severe laminary defects in some regions of the brain including the cerebral cortex and cerebellum. In vivo BrdU labeling and immunohistochemical analyses with specific markers suggested that the laminary abnormalities are a result of poorly regulated neuronal migration by a cell-autonomous mechanism. Analyses of cerebellar granule cells revealed that the BDNF-stimulated directional migration is impaired in Apc2-deficient cells. We found that APC2 is distributed along actin fibers as well as microtubules by TIRF microscopy, and that BDNF-stimulated F-actin formation at the leading edge is impaired in Apc2-deficient neurons due to the dysregulation of Rho GTPase activity. These results suggest that APC2 is an essential mediator of the cytoskeletal regulation at leading edges in response to extracellular signals.

大肠腺瘤性息肉病2 （APC2）主要表达于神经系统，并调节神经元的微管稳定性。我展示了Apc2缺失会导致大脑某些区域严重的层状缺损包括大脑皮层和小脑。体内BrdU标记和特定标记物的免疫组织化学分析表明，层状结构异常是细胞自主机制下神经元迁移调节不良的结果。对小脑颗粒细胞的分析显示，bdnf刺激的定向迁移在apc2缺陷细胞中受损。我们通过TIRF显微镜发现APC2沿肌动蛋白纤维和微管分布，并且由于Rho GTPase活性失调，在APC2缺陷的神经元中，bdnf刺激的前沿f -肌动蛋白形成受损。这些结果表明，APC2是细胞骨架在响应细胞外信号的前沿调控的重要介质。

项目成果

APC2は神経細胞の移動に必須である

APC2 对于神经元迁移至关重要

• 作者: 新谷隆史;竹内靖;藤川顕寛;野田昌晴
• 通讯作者: 野田昌晴

脳の層構造を作る分子

构成大脑层状结构的分子

• 发表时间: 2013
• 期刊: 化学と生物
• 作者: 新谷隆史;野田昌晴
• 通讯作者: 野田昌晴

SPIG1 negatively regulates BDNF maturation

SPIG1 负向调节 BDNF 成熟

• DOI: 10.1523/jneurosci.1597-13.2014
• 发表时间: 2014
• 期刊: J. Neurosci
• 作者: Suzuki R;Matsumoto M;Fujikawa A;Kato A;Kuboyama K;Yonehara K;Shintani T;Sakuta H;Noda M
• 通讯作者: Noda M

Substrate specificity of R3 receptor-like protein tyrosine phosphatase subfamily towards receptor protein tyrosine kinases

R3受体样蛋白酪氨酸磷酸酶亚家族对受体蛋白酪氨酸激酶的底物特异性

• DOI: 10.1074/jbc.m113.458489
• 发表时间: 2013
• 期刊: J. Biol. Chem
• 作者: Sakuraba J;Shintani T;Tani S;Noda M
• 通讯作者: Noda M

A distinct effect of transient and sustained upregulation of cellular factor XIII in the goldfish retina and optic nerve on optic nerve regeneration.

金鱼视网膜和视神经中细胞因子 XIII 的短暂和持续上调对视神经再生的明显影响。

• DOI: 10.1016/j.neuint.2012.06.004
• 发表时间: 2012
• 期刊: Neurochemistry International
• 影响因子: 4.2
• 作者: Sugitani;et al.
• 通讯作者: et al.