論文 - 詳細
| RRC ID | 47330 |
|---|---|
| 著者 | Kanoh H, Tong LL, Kuraishi T, Suda Y, Momiuchi Y, Shishido F, Kurata S. |
| タイトル | Genome-wide RNAi screening implicates the E3 ubiquitin ligase Sherpa in mediating innate immune signaling by Toll in Drosophila adults. |
| ジャーナル | 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. |
| 巻・号 | 8(400) |
| ページ | ra107 |
| 公開日 | 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 |
| 引用数 | 10 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 6 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
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