PUBLICATION

Nuclear S-nitrosylation impacts tissue regeneration in zebrafish

Authors
Matrone, G., Jung, S.Y., Choi, J.M., Jain, A., Leung, H.E., Rajapakshe, K., Coarfa, C., Rodor, J., Denvir, M.A., Baker, A.H., Cooke, J.P.
ID
ZDB-PUB-211103-4
Date
2021
Source
Nature communications   12: 6282 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Animal Fins/physiology*
  • Animals
  • Cell Nucleus/genetics
  • Cell Nucleus/metabolism*
  • Co-Repressor Proteins/genetics
  • Co-Repressor Proteins/metabolism
  • Female
  • Histone Demethylases/genetics
  • Histone Demethylases/metabolism
  • Male
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/metabolism
  • Nitric Oxide/metabolism*
  • Regeneration*
  • Signal Transduction
  • Tail/physiology*
  • Zebrafish/genetics
  • Zebrafish/physiology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
34725362 Full text @ Nat. Commun.
Abstract
Despite the importance of nitric oxide signaling in multiple biological processes, its role in tissue regeneration remains largely unexplored. Here, we provide evidence that inducible nitric oxide synthase (iNos) translocates to the nucleus during zebrafish tailfin regeneration and is associated with alterations in the nuclear S-nitrosylated proteome. iNos inhibitors or nitric oxide scavengers reduce protein S-nitrosylation and impair tailfin regeneration. Liquid chromatography/tandem mass spectrometry reveals an increase of up to 11-fold in the number of S-nitrosylated proteins during regeneration. Among these, Kdm1a, a well-known epigenetic modifier, is S-nitrosylated on Cys334. This alters Kdm1a binding to the CoRest complex, thus impairing its H3K4 demethylase activity, which is a response specific to the endothelial compartment. Rescue experiments show S-nitrosylation is essential for tailfin regeneration, and we identify downstream endothelial targets of Kdm1a S-nitrosylation. In this work, we define S-nitrosylation as an essential post-translational modification in tissue regeneration.
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