Deficiency in ubiquitin-like protein Ubl4A impairs migration of fibroblasts and macrophages

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• 作者：Yu Zhao ; Huaiyuan Zhang ; Carlos Affonso ; Raiza Bonomo ; Adriana Mañ ; as ; Jialing Xiang ; ^{xiang@iit.edu}
• 关键词：Ubl4A ; Actin ; Wound healing ; Cell migration ; Phagocytosis ; Lamellipodia
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2017
• 出版时间：29 January 2017
• 年：2017
• 卷：483
• 期：1
• 页码：617-623
• 全文大小：1890 K
• 卷排序：483

文摘

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 wild-type controls. These results imply an important role for Ubl4A in cell migration-associated pathophysiological processes.