ZFIN ID: ZDB-PUB-200426-14
Citrullination regulates wound responses and tissue regeneration in zebrafish
Golenberg, N., Squirrell, J.M., Bennin, D.A., Rindy, J., Pistono, P.E., Eliceiri, K.W., Shelef, M.A., Kang, J., Huttenlocher, A.
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.
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.