The SUMO-targeted ubiquitin ligase, Dgrn, is essential for Drosophila innate immunity

• DOI: 10.1387/ijdb.160250ao
• Publication Date: 2017-06-14T11:27:43Z
• Authors: Bella Koltun; Eliza Shackelford; François Bonnay; Nicolas Matt; Jean Marc Reichhart; Amir Orian
• Keywords: 0301 basic medicine; Cytoplasm; Genotype; Hydrolases; Gene Expression Profiling; NF-kappa B; Gene Expression Regulation, Developmental; Antibodies; Immunity, Innate; Cell Line; 3. Good health; 03 medical and health sciences; Enterocytes; Mutation; Animals; Drosophila Proteins; Drosophila; RNA Interference; Intestinal Mucosa; Crosses, Genetic; Antimicrobial Cationic Peptides; Plasmids; Signal Transduction

The ability of metazoans to combat pathogenic infection involves both systemic and local responses the invading pathogens. Ubiquitin SUMO pathways molecularly regulate response infection, immune signaling gene expression. Here, we report that Degringolade (Dgrn, CG10981), a SUMO-targeted ubiquitin ligase connecting two pathways, is essential for innate immunity in Drosophila. dgrnDK null heterozygous mutant adult flies are severely immune-compromised succumb rapidly bacteria fungi infections. sensitivity stems from inability produce multiple anti-microbial peptides, transcriptional analyses suggest overexpression Dgrn enhances output NF-ĸB related Toll deficiency (IMD)-pathways. Moreover, expression alleviated inhibitory impact cytoplasmic inhibitor Cactus nuclear co-repressor Groucho/TLE (Gro). Additionally, found required regenerative mid-gut following infection. Upon oral dgrn fail activate Delta-Notch pathway stem cells enteroblasts, unable regenerate replace damaged dying enterocytes. Interestingly, ubiquitin-specific protease CG8334 (dUSP32/dUSP11) antagonizes activity gut, halving dose restores rescues lethality observed mutants. Collectively, our data tissue