ATAXIN-2将猛龙捕获到聚合物中,并破坏细胞mTORC1信号传输
Ya-Jun Liu1,2, Jian-Yang Wang1,2, Xiang-Le Zhang1,2
1State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China.
The FEBS journal
|February 3, 2024
概括
ATAXIN-2蛋白质聚合隔离器Raptor,抑制mTORC1信号传递并诱导自. 这一发现揭示了脊髓小脑动症2型 (SCA2) 的病原性.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- ATAXIN-2 (Atx2) 是一种多重氨酸 (polyQ) 蛋白质,涉及到2型脊髓脑动性衰竭 (SCA2).
- Atx2聚合导致神经退行的确切机制尚不清楚.
- 了解Atx2在蛋白质病变中的作用对于开发治疗策略至关重要.
研究的目的:
- 阐明ATAXIN-2聚合的分子机制和细胞后果.
- 研究Atx2和mTORC1信号通路组件之间的相互作用.
- 探索Atx2聚合对自的影响.
主要方法:
- 利用分子和细胞生物学技术.
- 研究了Atx2和Raptor之间的蛋白质-蛋白质相互作用.
- 通过下游标记器评估mTORC1活动,例如化P70S6K.
- 监测的自标志物,包括LC3-II和酸化ULK1.1.
主要成果:
- 正常和扩展的Atx2都能将Raptor - - 猛素复合体1 (mTORC1) 成分的哺乳动物标 - - 隔离成聚合物.
- 亚特克斯2的多Q通道和N端区域 (残留1-784) 介导了猛龙捕获.
- 猛龙捕捉抑制mTORC1活动,由减少酸化P70S6K证明,这是猛龙过度表达可逆的.
- Atx2聚合会诱导自,由LC3-II增加和酸化ULK1.1减少表明.
结论:
- 素-2聚合封存猛龙,导致mTORC1信号受损和随后的自诱导.
- 这种机制提供了对2型脊髓小脑动症和其他多重质胺疾病的病原体的洞察.
- 这些发现突出了Atx2,mTORC1和神经退行过程中的自之间的一种新的联系.
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