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肌动蛋白结合蛋白 Adseverin 介导中性粒细胞的极化和迁移。

The actin-binding protein Adseverin mediates neutrophil polarization and migration.

机构信息

Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.

Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.

出版信息

Cytoskeleton (Hoboken). 2021 May;78(5):206-213. doi: 10.1002/cm.21684. Epub 2021 Aug 11.

DOI:10.1002/cm.21684
PMID:34370397
Abstract

Through the process of chemotactic migration, neutrophils are able to recruit to an inflammatory site and eliminate pathogens, thus playing a vital role in host defense. The process of neutrophil chemotaxis is mediated by dynamic actin reorganization and polymerization. Adseverin, an actin-binding protein and member of the Gelsolin superfamily of proteins, has been hypothesized to regulate goal directed movement through the capping and severing of actin filaments, but has never been investigated in the context of neutrophil chemotaxis. Using an Adseverin knockout mouse model, we show that Adseverin plays a role in subcortical F-actin assembly at the leading edge during chemotaxis through the generation of free barbed ends on existing actin filaments. In addition, in the absence of Adseverin, neutrophils show reduced speed of migration in vitro and in vivo. This study indicates that Adseverin is a regulator of actin filament generation during neutrophil chemotaxis.

摘要

通过趋化性迁移,中性粒细胞能够招募到炎症部位并消灭病原体,从而在宿主防御中发挥重要作用。中性粒细胞趋化作用的过程是由动态肌动蛋白重组和聚合介导的。Adseverin 是一种肌动蛋白结合蛋白,也是 Gelsolin 超家族蛋白的成员,它被假设通过肌动蛋白丝的加帽和切断来调节靶向运动,但从未在中性粒细胞趋化作用的背景下进行过研究。使用 Adseverin 敲除小鼠模型,我们表明 Adseverin 通过在现有肌动蛋白丝上生成游离的端帽,在趋化过程中发挥作用,在皮质下 F-actin 组装。此外,在缺乏 Adseverin 的情况下,中性粒细胞在体外和体内的迁移速度降低。这项研究表明,Adseverin 是中性粒细胞趋化过程中肌动蛋白丝生成的调节剂。

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The actin-binding protein Adseverin mediates neutrophil polarization and migration.肌动蛋白结合蛋白 Adseverin 介导中性粒细胞的极化和迁移。
Cytoskeleton (Hoboken). 2021 May;78(5):206-213. doi: 10.1002/cm.21684. Epub 2021 Aug 11.
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Comparison between the gelsolin and adseverin domain structure.凝溶胶蛋白和吸附蛋白结构域结构的比较。
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Murine adseverin (D5), a novel member of the gelsolin family, and murine adseverin are induced by interleukin-9 in T-helper lymphocytes.小鼠促解素(D5)是凝溶胶蛋白家族的一个新成员,小鼠促解素由辅助性T淋巴细胞中的白细胞介素-9诱导产生。
Mol Cell Biol. 1998 Aug;18(8):4589-96. doi: 10.1128/MCB.18.8.4589.
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The crystal structure of the C-terminus of adseverin reveals the actin-binding interface.促肌动蛋白收缩蛋白C末端的晶体结构揭示了肌动蛋白结合界面。
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Coordinated regulation of platelet actin filament barbed ends by gelsolin and capping protein.凝溶胶蛋白和封端蛋白对血小板肌动蛋白丝倒刺端的协同调节。
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Purification and properties of a Ca(2+)-independent barbed-end actin filament capping protein, CapZ, from human polymorphonuclear leukocytes.从人多形核白细胞中纯化及鉴定一种不依赖Ca(2+)的肌动蛋白丝尖端封端蛋白CapZ及其性质
Biochemistry. 1996 Mar 19;35(11):3518-24. doi: 10.1021/bi952470p.

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