通过异质的mTORC1和高的ERK激活在心肌细胞中的双转化控制
Keita Uchida1, Emily A Scarborough1, Benjamin L Prosser1
1Department of Physiology, Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
bioRxiv : the preprint server for biology
|February 24, 2025
概括
心脏缩包括由mTORC1.1调节的异质蛋白质合成. 一个新的MEK-ERK通路也控制心脏生长过程中的翻译,挑战现有的模型.
科学领域:
- 心血管生物学 心血管生物学
- 分子细胞生物学 分子细胞生物学
- 翻译条例 翻译条例
背景情况:
- 心脏缩是对血液动力学负荷增加的反应,但可能导致不良后果.
- 驱动心脏缩的翻译控制机制尚不清楚.
- 这项研究调查了在心脏平衡和过度增大期间各种转化控制机制的作用.
研究的目的:
- 阐明心肌细胞中转化控制机制的相对贡献.
- 了解这些机制如何在过度缩生长过程中适应.
- 在心脏适应过程中识别蛋白质合成的关键调节者.
主要方法:
- 使用了免疫光和单个肌细胞蛋白质合成试验.
- 在基底和缩条件下,在孤立的成年大鼠心肌细胞中检查了转化控制.
- 在小鼠模型中研究了烯诱导的心脏缩的机制.
主要成果:
- 在心肌细胞中观察到拉帕米辛复合物1 (mTORC1) 活性和蛋白质合成的异质机械标.
- 基线转换主要由mTORC1-依赖的4EBP1酸化调节.
- 烯刺激增加了mTORC1活动,并改变了4EBP1酸化模式,涉及一种新的MEK-ERK依赖途径.
结论:
- 心肌细胞中的蛋白质合成是异质的,由mTORC1活动的变化驱动.
- MEK-ERK信号直接影响4EBP1酸化,在心脏缩期间增强翻译.
- 这些发现挑战了心脏适应背景下翻译启动的正典模型.
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