罗效应器ARHGAP18通过YAP和默林协调Hippo路径反循环,以调节细胞骨和上皮细胞极性
bioRxiv : the preprint server for biology
|December 9, 2024
概括
这种RhoA效应器ARHGAP18连接了Hippo和Rho信号通路. 它的损失破坏了细胞活性细胞骨组织和YAP核定位,揭示了途径协调.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 动蛋白细胞骨组织对于细胞形态和极性至关重要.
- 两个关键的调节者是Rho家族GTPases和Hippo通路.
- 这些通路以前被认为是独立行动的.
研究的目的:
- 研究Hippo和Rho家族信号通路之间的相互作用.
- 确定协调这些actin调节通路的分子机制.
- 描述ARHGAP18在连接Hippo和Rho信号中的作用.
主要方法:
- 使用了人类上皮细胞.
- 在CRISPR/Cas9基因编辑中进行淘汰ARHGAP18.
- 超高分辨率的STORM显微镜用于分析actin细胞骨架.
- 生物化学测试以确定蛋白质复合体的形成.
主要成果:
- ARHGAP18与YAP形成一个复合体,这是Hippo路径转录因子.
- 失去ARHGAP18会导致异常的RhoA信号传递.
- ARHGAP18的淘汰会导致不适当的YAP核定位.
- 单片导线分析显示了显著的actin细胞骨变化.
结论:
- ARHGAP18充当RhoA和Hippo信号通路之间的关键纽带.
- 这些途径在调节actin细胞骨方面是协调的.
- 这些发现解决了关于独立的actin调节机制的.
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