Association between mitochondrial quality control and Parkinson's disease by FKBP38

FKBP38 线粒体质量控制与帕金森病之间的关联

• 批准号: 25640013
• 负责人: SHIRANE Michiko
• 金额: $ 2.58万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2013
• 资助国家: 日本
• 起止时间: 2013-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-25640013/
• 关键词: 病態脳科学; ミトコンドリア

Shh signaling pathway is conserved among animals and has pivotal roles in embryonic development, in the maintenance of adult stem cells, and in cancer. FKBP38 has been shown to act in a cell-autonomous manner to prevent inappropriate activation of the Shh pathway. It has remained unclear, however, how FKBP38 suppresses Shh signaling.With the use of a proteomics approach to the discovery of proteins that regulate Shh signaling in association with FKBP38, we have now identified ANKMY2 as a molecule that interacts with FKBP38. Depletion or overexpression of ANKMY2 resulted in down- and up-regulation of Shh signaling, respectively, in mouse embryonic fibroblasts. Furthermore, combined depletion of both FKBP38 and ANKMY2 attenuated Shh signaling in these cells, suggesting that ANKMY2 acts downstream of FKBP38 to activate the Shh signaling pathway. Our findings thus indicate that the FKBP38-ANKMY2 axis plays a key role in regulation of Shh signaling in vivo.

Shh信号通路在动物中是保守的，并且在胚胎发育、成体干细胞的维持和癌症中具有关键作用。FKBP 38已被证明以细胞自主方式起作用，以防止Shh通路的不适当激活。然而，FKBP 38如何抑制Shh信号传导仍不清楚，随着使用蛋白质组学方法发现与FKBP 38相关的调节Shh信号传导的蛋白质，我们现在已经确定ANKMY 2为与FKBP 38相互作用的分子。在小鼠胚胎成纤维细胞中，ANKMY 2的缺失或过表达分别导致Shh信号的下调和上调。此外，FKBP 38和ANKMY 2两者的联合消耗减弱了这些细胞中的Shh信号传导，表明ANKMY 2在FKBP 38下游起作用以激活Shh信号传导途径。因此，我们的研究结果表明，FKBP 38-ANKMY 2轴在体内Shh信号转导的调节中起着关键作用。

项目成果

ミトコンドリア品質管理機構と神経機能制御

线粒体质量控制机制与神经功能控制

• 发表时间: 2014
• 期刊: 「生化学」ミニレビュー
• 作者: Hashimoto;Y.;Shirane;M.;Matsuzaki;F.;Saita;S. Ohnishi;T.;and Nakayama;K. I.;白根道子
• 通讯作者: 白根道子

Identification and characterization of a neuron-specific isoform of protrudin

• DOI: 10.1111/gtc.12109
• 发表时间: 2014-02-01
• 期刊: GENES TO CELLS
• 影响因子: 2.1
• 作者: Ohnishi, Takafumi;Shirane, Michiko;Nakayama, Keiichi I.
• 通讯作者: Nakayama, Keiichi I.

Escape of proteins from mitochondria upon mitophagy

线粒体自噬时蛋白质从线粒体中逃逸

• 发表时间: 2012
• 作者: Yuya Fukano;Yuuya Tachiki;Tetsukazu Yahara;Yoh Iwasa;細田 將太郎
• 通讯作者: 細田 將太郎

Protrudin Regulates Endoplasmic Reticulum Morphology and Function Associated with the Pathogenesis of Hereditary Spastic Paraplegia

• DOI: 10.1074/jbc.m113.528687
• 发表时间: 2014-05-09
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Hashimoto, Yutaka;Shirane, Michiko;Nakayama, Keiichi I.
• 通讯作者: Nakayama, Keiichi I.

マイトファジーにおける選択的タンパク質脱出の発見と機構解析

线粒体自噬过程中选择性蛋白质逃逸的发现和机制分析

• 发表时间: 2013
• 期刊: 細胞工学
• 作者: 細田將太郎;白根道子;中山敬一
• 通讯作者: 中山敬一