RRC ID 6443
Author Ziegler K, Kurz CL, Cypowyj S, Couillault C, Pophillat M, Pujol N, Ewbank JJ.
Title Antifungal innate immunity in C. elegans: PKCdelta links G protein signaling and a conserved p38 MAPK cascade.
Journal Cell Host Microbe
Abstract Like other multicellular organisms, the model nematode C. elegans responds to infection by inducing the expression of defense genes. Among the genes upregulated in response to a natural fungal pathogen is nlp-29, encoding an antimicrobial peptide. In a screen for mutants that fail to express nlp-29 following fungal infection, we isolated alleles of tpa-1, homologous to the mammalian protein kinase C (PKC) delta. Through epistasis analyses, we demonstrate that C. elegans PKC acts through the p38 MAPK pathway to regulate nlp-29. This involves G protein signaling and specific C-type phospholipases acting upstream of PKCdelta. Unexpectedly and unlike in mammals, tpa-1 does not act via D-type protein kinases, but another C. elegans PKC gene, pkc-3, functions nonredundantly with tpa-1 to control nlp-29 expression. Finally, the tribbles-like kinase nipi-3 acts upstream of PKCdelta in this antifungal immune signaling cascade. These findings greatly expand our understanding of the pathways involved in C. elegans innate immunity.
Volume 5(4)
Pages 341-52
Published 2009-4-23
DOI 10.1016/j.chom.2009.03.006
PII S1931-3128(09)00097-3
PMID 19380113
MeSH Animals Caenorhabditis elegans / enzymology* Caenorhabditis elegans / immunology* Caenorhabditis elegans Proteins / immunology* Caenorhabditis elegans Proteins / metabolism* Fungi / immunology* GTP-Binding Proteins / metabolism Gene Expression Regulation, Fungal Immunity, Innate* Models, Biological Protein Kinase C / metabolism Protein-Tyrosine Kinases / immunology* Protein-Tyrosine Kinases / metabolism* Signal Transduction Type C Phospholipases / metabolism p38 Mitogen-Activated Protein Kinases / immunology
IF 17.872
Times Cited 59
C.elegans tm3036