Ubiquitin-Like Protein Ubl4a Promotes Actin-Mediated Cell Migration

Ubiquitin‐like protein Ubl4A is a small and multi‐functional protein with no ubiquitination activity. Ubl4A is involved in a broad range of cellular activities from C‐tail protein anchoring to tumor suppression. We have shown that Ubl4A is also critical for translocation of signaling protein and cell migration. Ubl4A directly interacts with Arp2/3 to accelerate actin branching, allowing Akt translocation from cytosol to plasma membrane for activation. Here we show that Ubl4A, F‐actin and Arp2/3 are also co‐localized at the cell leading edges during wound closure. Deficiency of Ubl4A significantly reduces actin‐mediated membrane protrusion, and cell migration for wound healing. In addition, the ability of fibroblasts to migrate out of corneal tissue ex vivo is also impaired in Ubl4A ‐deficient mice. Interestingly, cell motility, but not phagocytosis, is significantly decreased in Ubl4A ‐deficient macrophages. These results imply an important role for Ubl4A in regulation of cellular signaling and migration‐associated pathophysiological processes.