NLRC3-like 1 inhibits NOD1-RIPK2 pathway via targeting RIPK2

Fang, H., Wu, X.M., Hu, Y.W., Song, Y.J., Zhang, J., Chang, M.X.
Developmental and comparative immunology   112: 103769 (Journal)
Registered Authors
Chang, Mingxian
NLRC3-like, NOD1-RIPK2 pathway, Negative regulation, Proinflammatory cytokines, Zebrafish
MeSH Terms
  • Animals
  • Cells, Cultured
  • Cytokines/metabolism
  • Edwardsiella/physiology*
  • Enterobacteriaceae Infections/immunology*
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Immunomodulation
  • Inflammation Mediators/metabolism
  • Intracellular Signaling Peptides and Proteins/genetics
  • Intracellular Signaling Peptides and Proteins/metabolism*
  • NF-kappa B/metabolism
  • Nod1 Signaling Adaptor Protein/metabolism*
  • Receptor-Interacting Protein Serine-Threonine Kinases/metabolism*
  • Signal Transduction
  • Zebrafish/immunology
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
32634524 Full text @ Dev. Comp. Immunol.
Both NLRC3 and NOD1 belong to regulatory NLR subfamily based on their best-characterized function. In mammals, NLRC3 was reported to function by attenuating signaling cascades initiated by other families of PRRs. In teleosts, multiple NLRC3-like genes were identified through transcriptome sequencing. However, the functions of many NLRC3-like genes, especially the fish-specific NLRC3-like genes, remain unclear. In the present study, we report the functional characterization of a novel category of NLRC3-like proteins (named as NLRC3-like 1) from the zebrafish, which consists of a fish-specific FISNA, a conserved NACHT and five C-terminal LRRs domains. The expression of zebrafish NLRC3-like 1 was inducible in response to Edwardsiella piscicida infection. During bacterial infection, the in vitro and in vivo studies revealed that zebrafish NLRC3-like 1 overexpression facilitated bacterial growth and dissemination, together with the decreased survival rate of zebrafish larvae infected with E. piscicida. The attenuated response by zebrafish NLRC3-like 1 in response to bacterial infection were characterized by the impaired expression of antibacterial genes, proinflammatory cytokines and Nox genes. Furthermore, zebrafish NLRC3-like 1 interacted with the adaptor protein RIPK2 of NODs signaling via the FISNA (Fish-specific NACHT associated domain) and NACHT domains. However, the interaction between zebrafish NLRC3-like 1 and RIPK2 inhibited the assembly of the NOD1-RIPK2 complex. Importantly, zebrafish NLRC3-like 1 inhibited NOD1-mediated antibacterial activity, NF-κB and MAPK pathways and proinflammatory cytokine production. All together, these results firstly demonstrate that zebrafish NLRC3-like 1 inhibits NOD1-RIPK2 antibacterial pathway via targeting the adaptor protein RIPK2.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes