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GxcM-Fbp17/RacC-WASP signaling regulates polarized cortex assembly in migrating cells via Arp2/3
Journal of Cell Biology ( IF 7.4 ) Pub Date : 2023-04-03 , DOI: 10.1083/jcb.202208151
Dong Li 1, 2 , Yihong Yang 1 , Chenglin Lv 3 , Yingjie Wang 4 , Xiaoting Chao 1, 5 , Jiafeng Huang 5, 6 , Shashi P Singh 7 , Ye Yuan 1, 5 , Chengyu Zhang 1, 5 , Jizhong Lou 5, 8 , Pu Gao 5, 6 , Shanjin Huang 4 , Bo Li 3 , Huaqing Cai 1, 5
Affiliation  

The actin-rich cortex plays a fundamental role in many cellular processes. Its architecture and molecular composition vary across cell types and physiological states. The full complement of actin assembly factors driving cortex formation and how their activities are spatiotemporally regulated remain to be fully elucidated. Using Dictyostelium as a model for polarized and rapidly migrating cells, we show that GxcM, a RhoGEF localized specifically in the rear of migrating cells, functions together with F-BAR protein Fbp17, a small GTPase RacC, and the actin nucleation-promoting factor WASP to coordinately promote Arp2/3 complex-mediated cortical actin assembly. Overactivation of this signaling cascade leads to excessive actin polymerization in the rear cortex, whereas its disruption causes defects in cortical integrity and function. Therefore, apart from its well-defined role in the formation of the protrusions at the cell front, the Arp2/3 complex-based actin carries out a previously unappreciated function in building the rear cortical subcompartment in rapidly migrating cells.

中文翻译:

GxcM-Fbp17/RacC-WASP 信号通过 Arp2/3 调节迁移细胞中的极化皮层组装

富含肌动蛋白的皮质在许多细胞过程中发挥着重要作用。其结构和分子组成因细胞类型和生理状态而异。驱动皮质形成的肌动蛋白组装因子的完整补充以及它们的活动如何时空调节仍有待充分阐明。使用盘基网柄菌作为极化和快速迁移细胞的模型,我们发现 GxcM(一种专门位于迁移细胞后部的 RhoGEF)与 F-BAR 蛋白 Fbp17、一种小型 GTPase RacC 和肌动蛋白成核促进因子 WASP 一起发挥作用协调促进 Arp2/3 复合物介导的皮质肌动蛋白组装。这种信号级联的过度激活会导致后皮质肌动蛋白过度聚合,而其破坏则会导致皮质完整性和功能缺陷。因此,除了在细胞前部突起形成中明确的作用之外,基于 Arp2/3 复合物的肌动蛋白在快速迁移细胞中构建后部皮质亚区室中还发挥着以前未被认识到的功能。
更新日期:2023-04-03
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