title: The fatty acid synthase fasn-1 acts upstream of WNK and Ste20/GCK-VI kinases to modulate antimicrobial peptide expression in C. elegans epidermis.
abstract: An important part of the innate immune response of the nematode C. elegans to fungal infection is the rapid induction of antimicrobial peptide gene expression. One of these genes, nlp‑29, is expressed at a low level in adults under normal conditions. Its expression is up-regulated in the epidermis by infection with Drechmeria coniospora, but also by physical injury and by osmotic stress. For infection and wounding, the induction is dependent on a p38 MAP kinase cascade, but for osmotic stress, this pathway is not required. To characterize further the pathways that control the expression of nlp‑29, we carried out a genetic screen for negative regulatory genes. We isolated a number of Peni (peptide expression no infection) mutants and cloned one. It corresponds to fasn‑1, the nematode ortholog of vertebrate fatty acid synthase. We show here that a pathway involving fatty acid synthesis and the evolutionary conserved wnk‑1 and gck‑3/Ste20/GCK‑VI kinases modulates nlp‑29 expression in the C. elegans epidermis, independently of p38 MAPK signaling. The control of the antimicrobial peptide gene nlp‑29 thus links different physiological processes, including fatty acid metabolism, osmoregulation, maintenance of epidermal integrity and the innate immune response to infection.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy; Université de la Méditerranée; Marseille, France.
authors.forename: Kwang-Zin
authors.initials: KZ
authors.lastname: Lee
authors.forename: Marina
authors.initials: M
authors.lastname: Kniazeva
authors.forename: Min
authors.initials: M
authors.lastname: Han
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pujol
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Ewbank
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D004817:Epidermis / Q000276:immunology* / Q000378:metabolism; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006706:Homeostasis; D007113:Immunity, Innate; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000076204:WNK Lysine-Deficient Protein Kinase 1; D014882:Water-Electrolyte Balance; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D023181:Antimicrobial Cationic Peptides; D029742:Caenorhabditis elegans Proteins; D064429:Fatty Acid Synthases; D017346:Protein Serine-Threonine Kinases; D000076204:WNK Lysine-Deficient Protein Kinase 1; C527979:gck-3 protein, C elegans; C523715:wnk-1 protein, C elegans; D048051:p38 Mitogen-Activated Protein Kinases