Gautreau Alexis M, Fregoso Fred E, Simanov Gleb, Dominguez Roberto
Laboratoire de Biologie Structurale de la Cellule, CNRS, École Polytechnique, Institut Polytechnique de Paris, 91128 Palaiseau, France.
Department of Physiology and Biochemistry and Molecular Biophysics Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Trends Cell Biol. 2022 May;32(5):421-432. doi: 10.1016/j.tcb.2021.10.006. Epub 2021 Nov 23.
Arp2/3 complex is an actin filament nucleation and branching machinery conserved in all eukaryotes from yeast to human. Arp2/3 complex branched networks generate pushing forces that drive cellular processes ranging from membrane remodeling to cell and organelle motility. Several molecules regulate these processes by directly inhibiting or activating Arp2/3 complex and by stabilizing or disassembling branched networks. Here, we review recent advances in our understanding of Arp2/3 complex regulation, including high-resolution cryoelectron microscopy (cryo-EM) structures that illuminate the mechanisms of Arp2/3 complex activation and branch formation, and novel cellular pathways of branch formation, stabilization, and debranching. We also identify major gaps in our understanding of Arp2/3 complex inhibition and branch stabilization and disassembly.
Arp2/3复合体是一种肌动蛋白丝成核和分支机制,在从酵母到人类的所有真核生物中都保守存在。Arp2/3复合体分支网络产生推动力量,驱动从膜重塑到细胞和细胞器运动等一系列细胞过程。几种分子通过直接抑制或激活Arp2/3复合体以及稳定或拆解分支网络来调节这些过程。在这里,我们综述了我们对Arp2/3复合体调节理解的最新进展,包括阐明Arp2/3复合体激活和分支形成机制的高分辨率冷冻电子显微镜(cryo-EM)结构,以及分支形成、稳定和去分支的新细胞途径。我们还确定了在我们对Arp2/3复合体抑制以及分支稳定和拆解理解方面的主要差距。