National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences , Beijing, China.
Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei, China.
J Cell Biol. 2023 Jun 5;222(6). doi: 10.1083/jcb.202208151. Epub 2023 Apr 3.
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.
富含肌动蛋白的皮质在许多细胞过程中起着基本作用。其结构和分子组成在不同的细胞类型和生理状态下有所不同。目前仍需要充分阐明驱动皮质形成的完整肌动蛋白组装因子及其活性的时空调节方式。我们以极化和快速迁移的细胞为模型，使用粘菌作为模型，表明 RhoGEF GxcM 特异性定位于迁移细胞的后部，与 F-BAR 蛋白 Fbp17、小 GTPase RacC 和肌动蛋白成核促进因子 WASP 一起协调促进 Arp2/3 复合物介导的皮质肌动蛋白组装。该信号级联的过度激活会导致后部皮质中过多的肌动蛋白聚合，而其破坏会导致皮质完整性和功能缺陷。因此，除了在细胞前缘突起的形成中具有明确的作用外，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方面发挥了以前未被重视的作用。
