血管新生通过细胞内贸易的调节,通过细胞质二烯1轻中间链1介导
Dymonn Johnson1, Sarah Colijn1, Jahmiera Richee1
1Cell Biology and Physiology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110.
bioRxiv : the preprint server for biology
|June 21, 2024
概括
滴氨酸细胞质1轻中间链1 (LIC1) 通常限制血管生长. 失去LIC1功能会通过破坏VEGFR2受体降解,导致过度的血管生成.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 发展生物学 发展生物学
背景情况:
- 丁氨酸细胞质1轻中间链1 (LIC1) 对于丁氨酸电机复合体至关重要.
- LIC1调节Rab介导的内体体贩运,影响蛋白质降解和循环.
- 功能障碍的LIC1预计会破坏细胞货物运输和运动活动.
研究的目的:
- 研究LIC1在血管生成中的作用.
- 阐明LIC1调节内皮细胞功能的分子机制.
- 为了确定与dynein介导的贩运相关的血管生成的新型调节者.
主要方法:
- 生成并分析了一种斑马鱼突变的dynein细胞质1轻中间链1 (dync1li1).
- 使用LIC1缺乏的人体内皮细胞的实验室研究.
- 进行了体内实验,涉及内皮特异性的Rab11a表达和rilpl1/2中的突变.
主要成果:
- 斑马鱼突变体呈现出增加的血管生成.
- 缺乏LIC1的内皮细胞显示VEGFR2的升高,SRC酸化的增加,以及增强的Rab11中介循环.
- 内皮细胞Rab11a激活和RILPL1/2适应蛋白中的突变模仿了过度血管生成的表型.
结论:
- 与RILPL1/2一起,LIC1通过促进VEGFR2.2的溶酶体降解来限制血管生成.
- 破坏LIC1和RILPL1/2-介导的溶酶体向增强了Rab11依赖的循环,促进SRC信号和血管生成.
- 通过调节VEGFR2的贩运和降解,LIC1在控制血管生成方面发挥着至关重要的作用.
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