title: Deficiency in ubiquitin-like protein Ubl4A impairs migration of fibroblasts and macrophages.
abstract: 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.
authors.affiliation: Department of Biology, Illinois Institute of Technology, Chicago, IL 60616, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Biology, Illinois Institute of Technology, Chicago, IL 60616, USA.
authors.forename: Huaiyuan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Biology, Illinois Institute of Technology, Chicago, IL 60616, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Affonso
authors.affiliation: Department of Biology, Illinois Institute of Technology, Chicago, IL 60616, USA.
authors.forename: Raiza
authors.initials: R
authors.lastname: Bonomo
authors.affiliation: Department of Biology, Illinois Institute of Technology, Chicago, IL 60616, USA.
authors.forename: Adriana
authors.initials: A
authors.lastname: Mañas
authors.affiliation: Department of Biology, Illinois Institute of Technology, Chicago, IL 60616, USA. Electronic address: xiang@iit.edu.
authors.forename: Jialing
authors.initials: J
authors.lastname: Xiang
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D003315:Cornea / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology*; D007328:Insulin / Q000378:metabolism; D008264:Macrophages / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010587:Phagocytosis; D011554:Pseudopodia / Q000378:metabolism; D014452:Ubiquitins / Q000172:deficiency* / Q000235:genetics*; D014945:Wound Healing
chemical_list: D000199:Actins; D007328:Insulin; D014452:Ubiquitins; C000598887:Ubl4a protein, mouse
keywords: Actin; Cell migration; Lamellipodia; Phagocytosis; Ubl4A; Wound healing