调节LATS1和LATS2的电压依赖定位到粘附结的调节
Chamika De Silva1, Brian A Kelch1, Dannel McCollum1
1Department of Biochemistry & Molecular Biotechnology, UMass Chan Medical School, Worcester, Massachusetts, United States of America.
PloS one
|February 2, 2026
概括
LIMD1通过LIM域和LATS-LATCH动机招募激酶LATS1/2来粘附连接. 这种相互作用对于河马通路中的机械信号传导至关重要.
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:
- 河马信号通路调节器官大小,对发育至关重要.
- LIM域蛋白1 (LIMD1) 是Hippo通路的一个关键调节者.
- 在机械应变时,LIMD1将LATS1/2激酶绑定到粘附结 (AJs).
研究的目的:
- 阐明LIMD1结合和招募LATS1/2到AJs的分子机制.
- 定义LIMD1-LATS1/2相互作用和机械应变灵敏度所涉及的结构和功能领域.
主要方法:
- 通过AlphaFold建模来识别保存的图案.
- 生物化学测试以确认蛋白质相互作用.
- 细胞局部化研究评估蛋白质招募到AJs.
- 网站导向的突变发生,以调查域功能.
主要成果:
- LIMD1的LIM域足以用于AJ本地化和LATS1/2绑定.
- 招募LATS1到AJs需要LIM域和N终端内在无序区域 (IDR).
- LIMD1的LIM1和LIM2域对于LATS1 AJ定位至关重要.
- 在LIMD1中保存的LATS-LATCH基因调节了与LATS1/2的结合,对依赖菌株的招募至关重要.
- 单独的LATS-LATCH动机就足以进行LIMD1结合和AJ定位.
结论:
- LIMD1采用LATS1/2招募的双边机制,涉及LIM域-LATCH相互作用和N终端IDR.
- 这种机制可以了解机械信号是如何通过Hippo路径转换的.
- 这些发现突显了特定蛋白质与蛋白质相互作用在调节细胞信号传递以响应机械线索时的重要性.
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