title: Unusual regulation of a STAT protein by an SLC6 family transporter in C. elegans epidermal innate immunity.
abstract: The cuticle and epidermis of Caenorhabditis elegans provide the first line of defense against invading pathogens. Upon invasion by the fungal pathogen Drechmeria coniospora, C. elegans responds by upregulating the expression of antimicrobial peptides (AMPs) in the epidermis via activation of at least two pathways, a neuroendocrine TGF-β pathway and a p38 MAPK pathway. Here, we identify the sodium-neurotransmitter symporter SNF-12, a member of the solute carrier family (SLC6), as being essential for both these immune signaling pathways. We also identify the STAT transcription factor-like protein STA-2 as a direct physical interactor of SNF-12 and show that the two proteins function together to regulate AMP gene expression in the epidermis. Both SNF-12 and STA-2 act cell autonomously and specifically in the epidermis to govern the transcriptional response to fungal infection. These findings reveal an unorthodox mode of regulation for a STAT factor and highlight the molecular plasticity of innate immune signaling.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Case 906, 13288 Marseille, France.
authors.forename: Katja
authors.initials: K
authors.lastname: Dierking
authors.forename: Jolanta
authors.initials: J
authors.lastname: Polanowska
authors.forename: Shizue
authors.initials: S
authors.lastname: Omi
authors.forename: Ilka
authors.initials: I
authors.lastname: Engelmann
authors.forename: Marta
authors.initials: M
authors.lastname: Gut
authors.forename: Frederique
authors.initials: F
authors.lastname: Lembo
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Ewbank
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pujol
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000276:immunology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D004817:Epidermis / Q000276:immunology; D050485:GABA Plasma Membrane Transport Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006999:Hypocreales / Q000276:immunology; D007113:Immunity, Innate; D008954:Models, Biological; D011485:Protein Binding; D025941:Protein Interaction Mapping; D050791:STAT Transcription Factors / Q000378:metabolism*
chemical_list: D023181:Antimicrobial Cationic Peptides; D029742:Caenorhabditis elegans Proteins; D050485:GABA Plasma Membrane Transport Proteins; D050791:STAT Transcription Factors