Division of Molecular Cell Biology, Zoological Institute, Technische Universität Braunschweig, Spielmannstrasse 7, Braunschweig 38106, Germany.
Department of Cell Biology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, Braunschweig 38124, Germany.
Essays Biochem. 2019 Oct 31;63(5):483-495. doi: 10.1042/EBC20190015.
Cell migration is an essential process, both in unicellular organisms such as amoeba and as individual or collective motility in highly developed multicellular organisms like mammals. It is controlled by a variety of activities combining protrusive and contractile forces, normally generated by actin filaments. Here, we summarize actin filament assembly and turnover processes, and how respective biochemical activities translate into different protrusion types engaged in migration. These actin-based plasma membrane protrusions include actin-related protein 2/3 complex-dependent structures such as lamellipodia and membrane ruffles, filopodia as well as plasma membrane blebs. We also address observed antagonisms between these protrusion types, and propose a model - also inspired by previous literature - in which a complex balance between specific Rho GTPase signaling pathways dictates the protrusion mechanism employed by cells. Furthermore, we revisit published work regarding the fascinating antagonism between Rac and Rho GTPases, and how this intricate signaling network can define cell behavior and modes of migration. Finally, we discuss how the assembly of actin filament networks can feed back onto their regulators, as exemplified for the lamellipodial factor WAVE regulatory complex, tightly controlling accumulation of this complex at specific subcellular locations as well as its turnover.
细胞迁移是一个基本过程,单细胞生物如变形虫以及高度发达的多细胞生物如哺乳动物的个体或集体运动都依赖于细胞迁移。细胞迁移受多种活动的控制,这些活动结合了突起和收缩力,通常由肌动蛋白丝产生。在这里,我们总结了肌动蛋白丝组装和周转过程,以及各自的生化活性如何转化为参与迁移的不同突起类型。这些基于肌动蛋白的质膜突起包括肌动蛋白相关蛋白 2/3 复合物依赖性结构,如片状伪足和膜皱襞、丝状伪足以及质膜泡。我们还讨论了这些突起类型之间的观察到的拮抗作用,并提出了一个模型——也受到以前文献的启发——其中特定 Rho GTPase 信号通路的复杂平衡决定了细胞采用的突起机制。此外,我们重新审视了关于 Rac 和 Rho GTPases 之间迷人拮抗作用的已发表工作,以及这种复杂的信号网络如何定义细胞行为和迁移模式。最后,我们讨论了肌动蛋白丝网络的组装如何反馈到它们的调节剂,例如片状伪足因子 WAVE 调节复合物,它可以紧密控制该复合物在特定亚细胞位置的积累及其周转。