Document Detail

Spn1 regulates the GNBP3-dependent Toll signaling pathway in Drosophila melanogaster.
MedLine Citation:
PMID:  21576362     Owner:  NLM     Status:  MEDLINE    
The Drosophila genome encodes 29 serpins, most of unknown function. We show here that Spn1 is an active protease inhibitor of the serpin superfamily. Spn1 inhibits trypsin in vitro and regulates the Toll-mediated immune response in vivo. Expression of the Toll-dependent transcripts Drosomycin and IM1 is increased in Spn1 null mutants. Overexpression of Spn1 reduces the induction of Drosomycin upon immune challenge with fungi but not Gram-positive bacteria. Similar reductions in Drosomycin levels are observed in the psh, spz, and grass mutants of the Toll signaling pathway. These results support a role of Spn1 as a repressor of Toll activation upon fungal infection. Epistatic analysis places Spn1 upstream of Spätzle processing enzyme and Grass, in the fungal cell wall-activated side branch of the pathway. Overexpression of the pattern recognition receptor GNBP3 activates the β-1,3-glucan-sensitive side branch of the Toll pathway. The resultant increased Drosomycin level is reduced by concomitant overexpression of Spn1, confirming that Spn1 regulates the fungal cell wall side branch. Spn1 null mutants show altered susceptibility to fungal infection compared to the wild type, demonstrating a requirement for Spn1 in the fine regulation of the immune response.
Ane Fullaondo; Susana García-Sánchez; Arantza Sanz-Parra; Emma Recio; So Young Lee; David Gubb
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-05-16
Journal Detail:
Title:  Molecular and cellular biology     Volume:  31     ISSN:  1098-5549     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-06-30     Completed Date:  2011-10-07     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2960-72     Citation Subset:  IM    
CIC bioGUNE, Biscay Technology Park, Building 801A, 48160 Derio, Spain.
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MeSH Terms
Carrier Proteins / genetics,  metabolism*
Drosophila Proteins / genetics,  metabolism*
Drosophila melanogaster / immunology,  microbiology,  physiology*
Epistasis, Genetic
Fungi / immunology,  pathogenicity
Immunity, Innate
Mycoses / immunology
Protease Inhibitors / metabolism*
RNA Interference
Serpins / genetics,  metabolism*
Signal Transduction / physiology*
Survival Rate
Toll-Like Receptors / genetics,  metabolism*
Reg. No./Substance:
0/Carrier Proteins; 0/Drosophila Proteins; 0/GNBP3 protein, Drosophila; 0/Protease Inhibitors; 0/Serpins; 0/Spn1 protein, Drosophila; 0/Toll-Like Receptors; 159522-55-1/drosomycin protein, Drosophila

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