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缺乏功能性Arp2/3复合物的成纤维细胞的纳米级肌动蛋白网络表征

Nano-scale actin-network characterization of fibroblast cells lacking functional Arp2/3 complex.

作者信息

Anderson Karen L, Page Christopher, Swift Mark F, Suraneni Praveen, Janssen Mandy E W, Pollard Thomas D, Li Rong, Volkmann Niels, Hanein Dorit

机构信息

Bioinformatics and Structural Biology Program, Sanford-Burnham Medical Research Institute, La Jolla, CA, United States.

Department of Cell Biology, Johns Hopkins School of Medicine, Baltimore, MD, United States.

出版信息

J Struct Biol. 2017 Mar;197(3):312-321. doi: 10.1016/j.jsb.2016.12.010. Epub 2016 Dec 21.

Abstract

Arp2/3 complex is thought to be the primary protrusive force generator in cell migration by controlling the assembly and turnover of the branched filament network that pushes the leading edge of moving cells forward. However, mouse fibroblasts without functional Arp2/3 complex migrate at rates similar to wild-type cells, contradicting this paradigm. We show by correlative fluorescence and large-scale cryo-tomography studies combined with automated actin-network analysis that the absence of functional Arp2/3 complex has profound effects on the nano-scale architecture of actin networks. Our quantitative analysis at the single-filament level revealed that cells lacking functional Arp2/3 complex fail to regulate location-dependent fine-tuning of actin filament growth and organization that is distinct from its role in the formation and regulation of dendritic actin networks.

摘要

Arp2/3复合物被认为是细胞迁移过程中的主要突出力产生者,它通过控制分支丝状网络的组装和周转来推动移动细胞的前缘向前。然而,缺乏功能性Arp2/3复合物的小鼠成纤维细胞迁移速度与野生型细胞相似,这与该范式相矛盾。我们通过相关荧光和大规模冷冻断层扫描研究,并结合自动肌动蛋白网络分析表明,缺乏功能性Arp2/3复合物对肌动蛋白网络的纳米级结构有深远影响。我们在单丝水平上的定量分析表明,缺乏功能性Arp2/3复合物的细胞无法调节肌动蛋白丝生长和组织的位置依赖性微调,这与其在树突状肌动蛋白网络形成和调节中的作用不同。

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