Deficiency in ubiquitin like protein Ubl4A impairs migration of fibroblasts and macrophages
Deficiency in ubiquitin like protein Ubl4A impairs migration of fibroblasts and macrophages
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DOI：
10.1016/j.bbrc.2016.12.094
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发表时间：
2017-01-29
影响因子：
3.1
通讯作者：
Xiang, Jialing
中科院分区：
文献类型：
--
作者：
Zhao, Yu;Zhang, Huaiyuan;Xiang, Jialing
泛素样蛋白Ubl4A是一种小的、多功能的蛋白，没有泛素化活性。我们之前已经证明Ubl4A直接与肌动蛋白相关蛋白2/3复合物（Arp2/3）相互作用，促进Arp2/3依赖性肌动蛋白分支，从而在胰岛素刺激下加速蛋白激酶Akt的质膜易位。在这里，我们发现Ubl4A对质膜突出和细胞迁移至关重要。Ubl4A， F-actin和Arp2/3在伤口闭合时共定位于细胞边缘。敲除Ubl4A可显著减少肌动蛋白介导的膜突出，延缓小鼠胚胎成纤维细胞的伤口愈合。与此一致的是，在ubl4a缺陷小鼠中，成纤维细胞离体迁移出角膜组织的能力也受到损害。此外，与野生型对照相比，缺乏ubl4a的巨噬细胞的细胞运动性而非吞噬能力显著降低。这些结果表明Ubl4A在细胞迁移相关的病理生理过程中起重要作用。(C) 2016 Elsevier Inc.版权所有。
Ubiquitin-like protein Ubl4A is a small, multi-functional protein with no ubiquitination activity. We have previously demonstrated that Ubl4A directly interacts with actin-related protein 2/3 complex (Arp2/3) and promotes Arp2/3-dependent actin branching, thereby accelerating plasma membrane translocation of protein kinase Akt upon insulin stimulation. Here, we show that Ubl4A is critical for plasma membrane protrusion and cell migration. Ubl4A, F-actin and Arp2/3 are co-localized at the cell leading edges during wound closure. Knockout of Ubl4A significantly reduces actin-mediated membrane protrusion and delays wound healing by primary mouse embryonic fibroblasts. Consistently, the ability of fibroblasts to migrate out of corneal tissue ex vivo is also impaired in Ubl4A-deficient mice. Furthermore, cell motility, but not phagocytosis, is significantly decreased in Ubl4A-deficient macrophages compared with wildtype controls. These results imply an important role for Ubl4A in cell migration-associated pathophysiological processes. (C) 2016 Elsevier Inc. All rights reserved.