title: The pseudokinase NIPI-4 is a novel regulator of antimicrobial peptide gene expression.
abstract: Hosts have developed diverse mechanisms to counter the pathogens they face in their natural environment. Throughout the plant and animal kingdoms, the up-regulation of antimicrobial peptides is a common response to infection. In C. elegans, infection with the natural pathogen Drechmeria coniospora leads to rapid induction of antimicrobial peptide gene expression in the epidermis. Through a large genetic screen we have isolated many new mutants that are incapable of upregulating the antimicrobial peptide nlp-29 in response to infection (i.e. with a Nipi or 'no induction of peptide after infection' phenotype). More than half of the newly isolated Nipi mutants do not correspond to genes previously associated with the regulation of antimicrobial peptides. One of these, nipi-4, encodes a member of a nematode-specific kinase family. NIPI-4 is predicted to be catalytically inactive, thus to be a pseudokinase. It acts in the epidermis downstream of the PKC∂ TPA-1, as a positive regulator of nlp antimicrobial peptide gene expression after infection. It also controls the constitutive expression of antimicrobial peptide genes of the cnc family that are targets of TGFß regulation. Our results open the way for a more detailed understanding of how host defense pathways can be molded by environmental pathogens.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille University, UM2, Marseille, France.
authors.forename: Sid Ahmed
authors.initials: SA
authors.lastname: Labed
authors.forename: Shizue
authors.initials: S
authors.lastname: Omi
authors.forename: Martha
authors.initials: M
authors.lastname: Gut
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Ewbank
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pujol
mesh_terms: D000483:Alleles; D000818:Animals; D000890:Anti-Infective Agents / Q000378:metabolism*; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism*; D001203:Ascomycota / Q000502:physiology; D017173:Caenorhabditis elegans / Q000201:enzymology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004817:Epidermis / Q000201:enzymology; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000378:metabolism; D005786:Gene Expression Regulation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D029742:Caenorhabditis elegans Proteins; C516803:GPA-12 protein, C elegans; C095371:TPA-1 protein, C elegans; D011505:Protein-Tyrosine Kinases; D044365:GTP-Binding Protein alpha Subunits, G12-G13