PUBLICATION

Citrullination regulates wound responses and tissue regeneration in zebrafish

Authors
Golenberg, N., Squirrell, J.M., Bennin, D.A., Rindy, J., Pistono, P.E., Eliceiri, K.W., Shelef, M.A., Kang, J., Huttenlocher, A.
ID
ZDB-PUB-200426-14
Date
2020
Source
The Journal of cell biology   219(4): (Journal)
Registered Authors
Huttenlocher, Anna, Kang, Junsu
Keywords
none
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Calcium/metabolism
  • Citrullination*
  • Histones/metabolism
  • Humans
  • Larva/growth & development
  • Protein-Arginine Deiminase Type 2/deficiency
  • Protein-Arginine Deiminase Type 2/genetics
  • Protein-Arginine Deiminase Type 2/metabolism*
  • Regeneration*
  • Sequence Alignment
  • Wound Healing*
  • Zebrafish/physiology*
PubMed
32328635 Full text @ J. Cell Biol.
Abstract
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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