瑞克托是一种mTORC2蛋白,通过AKT-FOXO1信号调节小鼠淋巴的形成
Richa Banerjee1, Luz A Knauer1, Drishya Iyer1
1Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa.
Arteriosclerosis, thrombosis, and vascular biology
|August 1, 2024
概括
拉巴胺素复合体2 (mTORC2) 的哺乳动物点对于淋巴形成至关重要. 通过激活AKT和抑制FOXO1,RICTOR可以促进淋巴的生长和维护.
科学领域:
- 血管生物学 血管生物学
- 细胞信号传递 细胞信号传递
- 机械生物学 机械生物学
背景情况:
- 淋巴对于防止淋巴回流至关重要,它们的正确形成对于预防先天性淋巴胀至关重要.
- 淋巴发育受到PI3K/AKT通路的调节,以应对剪切应力.
- 哺乳动物目标拉巴胺素复合体2 (mTORC2) 在淋巴形成中的作用以前是未知的.
研究的目的:
- 研究mTORC2的关键组成部分RICTOR在淋巴发育中的作用.
- 阐明RICTOR影响淋巴形成的信号机制.
主要方法:
- 利用体内和体外技术来研究淋巴内皮.
- 在小鼠中进行了Rictor的胚胎和产后淋巴切除.
- 在人类皮肤淋巴内皮细胞中进行RICTOR敲击.
- 分析了AKT活动,基因表达和FOXO1核定位.
主要成果:
- 里克托的淋巴切除显著减少了淋巴,并损害了收集淋巴血管的成熟.
- RICTOR knockdown降低了AKT激活和形成基因表达,消除了对剪切应激的反应.
- 里克托缺乏导致核FOXO1活性增加,这是一个抑制门形成的抑制剂.
- 在Rictor缺陷小鼠中删除Foxo1,挽救了淋巴形成.
结论:
- 确定了RICTOR在调节淋巴形成的机械传导途径中的新作用.
- 瑞克托激活了AKT,这反过来又抑制了核FOXO1的积累,促进了淋巴的发育和维护.
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