Reference - Detail
RRC ID | 47330 |
---|---|
Author | Kanoh H, Tong LL, Kuraishi T, Suda Y, Momiuchi Y, Shishido F, Kurata S. |
Title | Genome-wide RNAi screening implicates the E3 ubiquitin ligase Sherpa in mediating innate immune signaling by Toll in Drosophila adults. |
Journal | Sci Signal |
Abstract |
The Drosophila Toll pathway plays important roles in innate immune responses against Gram-positive bacteria and fungi. To identify previously uncharacterized components of this pathway, we performed comparative, ex vivo, genome-wide RNA interference screening. In four screens, we overexpressed the Toll adaptor protein dMyd88, the downstream kinase Pelle, or the nuclear factor κB (NF-κB) homolog Dif, or we knocked down Cactus, the Drosophila homolog of mammalian inhibitor of NF-κB. On the basis of these screens, we identified the E3 ubiquitin ligase Sherpa as being necessary for the activation of Toll signaling. A loss-of-function sherpa mutant fly exhibited compromised production of antimicrobial peptides and enhanced susceptibility to infection by Gram-positive bacteria. In cultured cells, Sherpa mediated ubiquitylation of dMyd88 and Sherpa itself, and Sherpa and Drosophila SUMO (small ubiquitin-like modifier) were required for the proper membrane localization of an adaptor complex containing dMyd88. These findings highlight a role for Sherpa in Drosophila host defense and suggest the SUMOylation-mediated regulation of dMyd88 functions in Toll innate immune signaling. |
Volume | 8(400) |
Pages | ra107 |
Published | 2015-10-27 |
DOI | 10.1126/scisignal.2005971 |
PII | 8/400/ra107 |
PMID | 26508789 |
MeSH | Animals Drosophila Proteins / genetics Drosophila Proteins / immunology* Drosophila melanogaster Genome-Wide Association Study Gram-Positive Bacteria / genetics Gram-Positive Bacteria / immunology* Gram-Positive Bacterial Infections / genetics Gram-Positive Bacterial Infections / immunology* Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / immunology RNA, Small Interfering / genetics RNA, Small Interfering / immunology* SUMO-1 Protein / genetics SUMO-1 Protein / immunology Toll-Like Receptors / genetics Toll-Like Receptors / immunology* Ubiquitin-Protein Ligases / genetics Ubiquitin-Protein Ligases / immunology* |
IF | 6.467 |
Times Cited | 10 |
WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
Resource | |
Drosophila |