PUBLICATION

RIP2 Is a Critical Regulator for NLRs Signaling and MHC Antigen Presentation but Not for MAPK and PI3K/Akt Pathways

Authors
Wu, X.M., Chen, W.Q., Hu, Y.W., Cao, L., Nie, P., Chang, M.X.
ID
ZDB-PUB-180426-16
Date
2018
Source
Frontiers in immunology   9: 726 (Journal)
Registered Authors
Cao, Lu, Chang, Mingxian, Nie, Pin
Keywords
MHC antigen presentation, NLRs signaling, RIP2 deficiency, larval survival, signaling pathways, transcriptome analysis
MeSH Terms
  • Animals
  • Antigen Presentation
  • Edwardsiella
  • Enterobacteriaceae Infections/immunology
  • Enterobacteriaceae Infections/veterinary
  • Fish Diseases/immunology
  • Histocompatibility Antigens/immunology
  • Larva
  • Mitogen-Activated Protein Kinases/immunology
  • Nod1 Signaling Adaptor Protein/immunology*
  • Phosphatidylinositol 3-Kinases/immunology
  • Proto-Oncogene Proteins c-akt/immunology
  • Receptor-Interacting Protein Serine-Threonine Kinase 2/genetics
  • Receptor-Interacting Protein Serine-Threonine Kinase 2/immunology*
  • Signal Transduction
  • Zebrafish
  • Zebrafish Proteins/immunology*
(all 17)
PubMed
29692779 Full text @ Front Immunol
Abstract
RIP2 is an adaptor protein which is essential for the activation of NF-κB and NOD1- and NOD2-dependent signaling. Although NOD-RIP2 axis conservatively existed in the teleost, the function of RIP2 was only reported in zebrafish, goldfish, and rainbow trout in vitro. Very little is known about the role and mechanisms of piscine NOD-RIP2 axis in vivo. Our previous study showed the protective role of zebrafish NOD1 in larval survival through CD44a-mediated activation of PI3K-Akt signaling. In this study, we examined whether RIP2 was required for larval survival with or without pathogen infection, and determined the signaling pathways modulated by RIP2. Based on our previous report and the present study, our data demonstrated that NOD1-RIP2 axis was important for larval survival in the early ontogenesis. Similar to NOD1, RIP2 deficiency significantly affected immune system processes. The significantly enriched pathways were mainly involved in immune system, such as "Antigen processing and presentation" and "NOD-like receptor signaling pathway" and so on. Furthermore, both transcriptome analysis and qRT-PCR revealed that RIP2 was a critical regulator for expression of NLRs (NOD-like receptors) and those genes involved in MHC antigen presentation. Different from NOD1, the present study showed that NOD1, but not RIP2 deficiency significantly impaired protein levels of MAPK pathways. Although RIP2 deficiency also significantly impaired the expression of CD44a, the downstream signaling of CD44a-Lck-PI3K-Akt pathway remained unchanged. Collectively, our works highlight the similarity and discrepancy of NOD1 and RIP2 in the regulation of immune signaling pathways in the zebrafish early ontogenesis, and confirm the crucial role of RIP2 in NLRs signaling and MHC antigen presentation, but not for MAPK and PI3K/Akt pathways.
Genes / Markers
Marker Marker Type Name
b2mGENEbeta-2-microglobulin
cd44aGENECD44 molecule (IN blood group) a
cd74aGENECD74 molecule, major histocompatibility complex, class II invariant chain a
ctss2.2GENEcathepsin S, ortholog 2, tandem duplicate 2
dhrs13b.2GENEdehydrogenase/reductase (SDR family) member 13b.2
hsp70.3GENEheat shock cognate 70-kd protein, tandem duplicate 3
lckGENELCK proto-oncogene, Src family tyrosine kinase
mhc1zkaGENEmajor histocompatibility complex class I ZKA
mhc2blGENEMHC class II beta chain-like
mhc2daaGENEmajor histocompatibility complex class II DAA gene
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Figures
Figure Gallery (1 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
AB/TUbacterial treatment by exposure to environment: Edwardsiella piscicidaDays 7-13
nod1ihb52/ihb52 (AB/TU)standard conditionsDays 7-13
nod1ihb52/ihb52 (AB/TU)standard conditionsDays 7-13
nod1ihb52/ihb52 (AB/TU)standard conditionsDays 7-13
nod1ihb52/ihb52 (AB/TU)standard conditionsDays 7-13
nod1ihb52/ihb52 (AB/TU)standard conditionsDays 7-13
nod1ihb52/ihb52 (AB/TU)standard conditionsDays 7-13
ripk2ihb47/ihb47 (AB/TU)standard conditionsPrim-5 to Days 7-13
ripk2ihb47/ihb47 (AB/TU)standard conditionsLong-pec
ripk2ihb47/ihb47 (AB/TU)standard conditionsLong-pec to Day 5
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ihb47
    		Indel
    ihb52
      		Insertion
      1 - 2 of 2
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      Human Disease / Model
      No data available
      Sequence Targeting Reagents
      Target Reagent Reagent Type
      ripk2CRISPR1-ripk2CRISPR
      1 - 1 of 1
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      Fish
      Fish
      AB/TU
      nod1ihb52/ihb52 (AB/TU)
      ripk2ihb47/ihb47 (AB/TU)
      1 - 3 of 3
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      Antibodies
      Orthology
      Engineered Foreign Genes
      No data available
      Mapping
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      Citation
      Wu, X.M., Chen, W.Q., Hu, Y.W., Cao, L., Nie, P., Chang, M.X. (2018) RIP2 Is a Critical Regulator for NLRs Signaling and MHC Antigen Presentation but Not for MAPK and PI3K/Akt Pathways. Frontiers in immunology. 9:726.