Journal
JOURNAL OF CELL BIOLOGY
Volume 219, Issue 4, Pages -Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201908164
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Funding
- National Institutes of Health [R35 GM1 18027, T32-GM07215, AHA16SDG30020001]
- National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases [AR065500]
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Calcium is an important early signal in wound healing, yet how these early signals promote regeneration remains unclear. Peptidylarginine deiminases (PADs), a family of calcium-dependent enzymes, catalyze citrullination, a post-translational modification that alters protein function and has been implicated in autoimmune diseases. We generated a mutation in the single zebrafish ancestral pad gene, padi2, that results in a loss of detectable calcium-dependent citrullination. The mutants exhibit impaired resolution of inflammation and regeneration after caudal fin transection. We identified a new subpopulation of cells displaying citrullinated histones within the notochord bead following tissue injury. Citrullination of histones in this region was absent, and wound-induced proliferation was perturbed in Padi2-deficient larvae. Taken together, our results show that Padi2 is required for the citrullination of histones within a group of cells in the notochord bead and for promoting wound-induced proliferation required for efficient regeneration. These findings identify Padi2 as a potential intermediary between early calcium signaling and subsequent tissue regeneration.
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