The receptor guanylate cyclase Gyc76C and a peptide ligand, NPLP1-VQQ, modulate the innate immune IMD pathway in response to salt stress

Overend, G. , Cabrero, P. , Guo, A.X., Sebastian, S., Cundall, M., Armstrong, H., Mertens, I., Schoofs, L., Dow, J.A.T. and Davies, S.-A. (2012) The receptor guanylate cyclase Gyc76C and a peptide ligand, NPLP1-VQQ, modulate the innate immune IMD pathway in response to salt stress. Peptides, 34(1), pp. 209-218. (doi:10.1016/j.peptides.2011.08.019)

Overend, G. , Cabrero, P. , Guo, A.X., Sebastian, S., Cundall, M., Armstrong, H., Mertens, I., Schoofs, L., Dow, J.A.T. and Davies, S.-A. (2012) The receptor guanylate cyclase Gyc76C and a peptide ligand, NPLP1-VQQ, modulate the innate immune IMD pathway in response to salt stress. Peptides, 34(1), pp. 209-218. (doi:10.1016/j.peptides.2011.08.019)

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Publisher's URL: http://dx.doi.org/10.1016/j.peptides.2011.08.019

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cundall, Dr Maria and Cabrero, Mr Pablo and Sebastian, Mr Sujith and Overend, Dr Gayle and Dow, Professor Julian and Davies, Professor Shireen
Authors: Overend, G., Cabrero, P., Guo, A.X., Sebastian, S., Cundall, M., Armstrong, H., Mertens, I., Schoofs, L., Dow, J.A.T., and Davies, S.-A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Peptides
ISSN:0196-9781
ISSN (Online):1873-5169
Published Online:27 August 2011

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
438361Cyclic nucleotide signalling in innate immunityShireen DaviesBiotechnology and Biological Sciences Research Council (BBSRC)BB/E011438/1Institute of Molecular Cell and Systems Biology
433611Genetic, proteomic and functional analysis of junctional complexes in DrosophilaJulian DowBiotechnology and Biological Sciences Research Council (BBSRC)BB/F021240/1Institute of Molecular Cell and Systems Biology