title: The receptor guanylate cyclase Gyc76C and a peptide ligand, NPLP1-VQQ, modulate the innate immune IMD pathway in response to salt stress.
abstract: Receptorguanylate cyclases (rGCs) modulate diverse physiological processes including mammalian cardiovascular function and insect eclosion. The Drosophila genome encodes several receptor and receptor-like GCs, but no ligand for any Drosophila rGC has yet been identified. By screening peptide libraries in Drosophila S2 cells, the Drosophila peptide NPLP1-VQQ (NLGALKSSPVHGVQQ) was shown to be a ligand for the rGC, Gyc76C (CG42636, previously CG8742, l(3)76BDl, DrGC-1). In the adult fly, expression of Gyc76C is highest in immune and stress-sensing epithelial tissues, including Malpighian tubules and midgut; and NPLP1-VQQ stimulates fluid transport and increases cGMP content in tubules. cGMP signaling is known to modulate the activity of the IMD innate immune pathway in tubules via activation and nuclear translocation of the NF-kB orthologue, Relish, resulting in increased anti-microbial peptide (AMP) gene expression; and so NPLP1-VQQ might act in immune/stress responses. Indeed, NPLP1-VQQ induces nuclear translocation of Relish in intact tubules and increases expression of the anti-microbial peptide gene, diptericin. Targeted Gyc76C RNAi to tubule principal cells inhibited both NPLP1-VQQ-induced Relish translocation and diptericin expression. Relish translocation and increased AMP gene expression also occurs in tubules in response to dietary salt stress. Gyc76C also modulates organismal survival to salt stress - ablation of Gyc76C expression in only tubule principal cells prevents Relish translocation, reduces diptericin expression, and reduces organismal survival in response to salt stress. Thus, the principal-cell localized NPLP1-VQQ/Gyc76C cGMP pathway acts to signal environmental (salt) stress to the whole organism.
authors: Institute of Molecular, Cell and Systems Biology, University of Glasgow, Glasgow, Scotland, UK.
authors: Gayle
authors: G
authors: Overend
authors: Pablo
authors: P
authors: Cabrero
authors: Andy Xin
authors: AX
authors: Guo
authors: Sujith
authors: S
authors: Sebastian
authors: Maria
authors: M
authors: Cundall
authors: Harry
authors: H
authors: Armstrong
authors: Inge
authors: I
authors: Mertens
authors: Liliane
authors: L
authors: Schoofs
authors: Julian A T
authors: JA
authors: Dow
authors: Shireen-A
authors: SA
authors: Davies
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000235:genetics / Q000378:metabolism*; D007113:Immunity, Innate / Q000187:drug effects* / Q000235:genetics; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000378:metabolism* / Q000494:pharmacology; D012965:Sodium Chloride / Q000494:pharmacology*
chemical_list: D029721:Drosophila Proteins; D009479:Neuropeptides; D012965:Sodium Chloride; D006162:Guanylate Cyclase