SGT1 is essential for Nod1 activation

Yan²,

Proc. Natl. Acad. Sci. U.S.A.

et al. 2010

130

152

Olfactomedin 4 (OLFM4) is a glycoprotein that has been found to be up-regulated in inflammatory bowel diseases and Helicobacter pylori infected patients. However, its role in biological processes such as inflammation or other immune response is not known. In this study, we generated OLFM4 KO mice to investigate potential role(s) of OLFM4 in gastric mucosal responses to H. pylori infection. H. pylori colonization in the gastric mucosa of OLFM4 KO mice was significantly lower compared with WT littermates. The reduced bacterial load was associated with enhanced infiltration of inflammatory cells in gastric mucosa. Production and expression of proinflammatory cytokines/chemokines such as IL-1β, IL-5, IL-12 p70, and MIP-1α was increased in OLFM4 KO mice compared with infected controls. Furthermore, we found that OLFM4 is a target gene of NF-κB pathway and has a negative feedback effect on NF-κB activation induced by H. pylori infection through a direct association with nucleotide oligomerization domain-1 (NOD1) and -2 (NOD2). Together these observations indicate that OLFM4 exerts considerable influence on the host defense against H. pylori infection acting through NOD1 and NOD2 mediated NF-κB activation and subsequent cytokines and chemokines production, which in turn inhibit host immune response and contribute to persistence of H. pylori colonization.NF-κB | nucleotide oligomerization domain-1 and -2

Section: Discussionmentioning

confidence: 99%

Olfactomedin 4 down-regulates innate immunity against Helicobacter pylori infection

Yan²,

Proc. Natl. Acad. Sci. U.S.A.

et al. 2010

130

152

“…Unlike bE119G, none of the DN mutants in SGSb was able to confer recovery of Rx protein accumulation to wild-type levels (see Supplemental Figure 7 online). The SGS domain is predicted to be the interaction domain for certain LRR proteins, including NBS-LRR proteins Mla1 from barley and human Nod1 (Dubacq et al, 2002;Bieri et al, 2004;da Silva Correia et al, 2007). Thus, we are currently investigating how these SGS mutations affect the formation and/or activation of R protein complexes.…”

Section: Cs and Sgs Domains Are Required For Rx Resistancementioning

confidence: 99%

Structural and Functional Analysis of SGT1 Reveals That Its Interaction with HSP90 Is Required for the Accumulation of Rx, an R Protein Involved in Plant Immunity

et al. 2007

SGT1 (for suppressor of G2 allele of skp1) and RAR1 (for required for Mla12 resistance) are highly conserved eukaryotic proteins that interact with the molecular chaperone HSP90 (for heat shock protein90). In plants, SGT1, RAR1, and HSP90 are essential for disease resistance triggered by a number of resistance (R) proteins. Here, we present structural and functional characterization of plant SGT1 proteins. Random mutagenesis of Arabidopsis thaliana SGT1b revealed that its CS (for CHORD-SGT1) and SGS (for SGT1 specific) domains are essential for disease resistance. NMR-based interaction surface mapping and mutational analyses of the CS domain showed that the CHORD II domain of RAR1 and the N-terminal domain of HSP90 interact with opposite sides of the CS domain. Functional analysis of the CS mutations indicated that the interaction between SGT1 and HSP90 is required for the accumulation of Rx, a potato (Solanum tuberosum) R protein.Biochemical reconstitution experiments suggest that RAR1 may function to enhance the SGT1-HSP90 interaction by promoting ternary complex formation.

“…In addition to structural similarities, NLRs and NB-LRRs have shared function and their stability is regulated by a chaperone complex containing HSP90 and SGT1. [11][12][13] Both NB-LRRs in plants and NLRs in mammals are classified according to their N-terminal domain architecture. Two main classes of plant NB-LRRs have been described: CC-NB-LRRs contain a predicted coiled-coil N-terminal domain and TIR-NB-LRRs carry N-terminal homology to the intracellular TIR domain of TLRs.…”

Section: Immune Surveillance Systems In Plants and Animalsmentioning

confidence: 99%

Programmed cell death in the plant immune system

2011

Cell death has a central role in innate immune responses in both plants and animals. Besides sharing striking convergences and similarities in the overall evolutionary organization of their innate immune systems, both plants and animals can respond to infection and pathogen recognition with programmed cell death. The fact that plant and animal pathogens have evolved strategies to subvert specific cell death modalities emphasizes the essential role of cell death during immune responses. The hypersensitive response (HR) cell death in plants displays morphological features, molecular architectures and mechanisms reminiscent of different inflammatory cell death types in animals (pyroptosis and necroptosis). In this review, we describe the molecular pathways leading to cell death during innate immune responses. Additionally, we present recently discovered caspase and caspase-like networks regulating cell death that have revealed fascinating analogies between cell death control across both kingdoms.