Research ArticleImmunology

Genome-wide RNAi screening implicates the E3 ubiquitin ligase Sherpa in mediating innate immune signaling by Toll in Drosophila adults

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Science Signaling  27 Oct 2015:
Vol. 8, Issue 400, pp. ra107
DOI: 10.1126/scisignal.2005971

Sherpa guides Toll signaling

Mammalian Toll-like receptors (TLRs) recognize pathogen-derived molecular patterns and stimulate the innate immune response. These proteins are named for their counterparts in the fruit fly Drosophila in which the first of these, Toll, was identified. Kanoh et al. showed that the fly Toll innate immune signaling pathway required an E3 ubiquitin ligase called Sherpa. Flies expressing a ligase-defective mutant Sherpa had compromised immune responses to bacterial infection. The adaptor protein dMyd88, which interacts with Toll, relied on both Sherpa and the Drosophila SUMO homolog for proper subcellular localization. Thus, this study reveals additional similarities between the fly and mammalian innate immune systems.