通过跨细胞伴侣信号传递来调节生物蛋白质稳定
Patricija van Oosten-Hawle1, Robert S Porter, Richard I Morimoto
1Department Molecular Biosciences, Rice Institute for Biomedical Research, Northwestern University, Evanston, IL 60208, USA.
Cell
|June 11, 2013
概括
生物通过全身应激反应来维持蛋白质健康. 在一个组织中增强热冲击蛋白90 (HSP90) 可以保护其他组织,揭示一个跨细胞监控系统.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 超生态动物面临的挑战是,尽管有各种各样的组织特异性蛋白质,但仍然需要维持生物体的蛋白质稳定.
- 蛋白质毒性压力可能来自错误折叠的蛋白质,威胁到细胞和生物体的健康.
- 像热冲击蛋白90 (HSP90) 一样,陪伴蛋白对于适当的蛋白质折叠至关重要.
研究的目的:
- 为了研究元动物中系统性蛋白质稳定的机制.
- 为了确定局部蛋白质错误折叠是否可以诱导整个生物体的应激反应.
- 阐明HSP90和细胞间通信在维持蛋白质稳定中的作用.
主要方法:
- 使用C. elegans作为模型生物来研究蛋白质折叠和应激反应.
- 诱导肌肉细胞中转移性蛋白质的表达,以模仿蛋白质毒性压力.
- 在不同组织 (肌肉,肠道,神经元) 中操纵HSP90表达.
- 研究了PHA-4转录因子在调节HSP90表达中的作用.
主要成果:
- 肌肉细胞中转移性蛋白质的表达触发了多种组织的全身应激反应.
- 在肌肉,肠道或神经细胞中增强的HSP90表达有效地抑制了肌肉中的蛋白质错折.
- 这种非细胞自主控制HSP90是由PHA-4转录因子调节的转录反介导的.
- 证明了一种对生物体蛋白质稳定至关重要的跨细胞伴侣信号通路.
结论:
- 局部蛋白质错误折叠可以诱导全身,细胞非自主伴侣反应.
- 由PHA-4调节的组织间通信对于维持生物体蛋白质稳定至关重要.
- 这种跨细胞信号提供了生物体应激感应监测的基础.
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