Drosophila Toll signaling regulated by novel E3 ligase Sherpa

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08267
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Kanazawa University
• Principal Investigator: Kuraishi Takayuki 金沢大学, 薬学系, 准教授 (90613167)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: Toll経路

Outline of Final Research Achievements

The Drosophila Toll pathway is involved in embryonic development, innate immunity, and cell-cell interactions. However, compared to the mammalian Toll-like receptor innate immune pathway, its intracellular signaling mechanisms are not fully understood. We have previously performed a series of ex vivo genome-wide RNAi screenings to identify genes required for the activation of the Toll pathway. In this study, we have conducted an additional genome-wide RNAi screening using the overexpression of Tube, an adapter molecule in the Toll pathway, and have performed a co-immunoprecipitation assay to identify components present in the dMyd88-Tube complex. Based on the results of these assays, we have performed a bioinformatic analysis, and describe candidate molecules and post-translational modifications that could be involved in Drosophila Toll signaling.

Free Research Field

自然免疫

Academic Significance and Societal Importance of the Research Achievements

自然免疫系は微生物感染に対する生体防御反応として重要であるが、その活性化を導くシグナル伝達機構はまだ充分明らかになっていない。本研究では、一連のゲノムワイドRNAiスクリーニングとバイオインフォマティクス解析により、ショウジョウバエ自然免疫経路であるTollシグナル伝達経路に関与するプロテインキナーゼ等の候補分子、さらにはTollシグナル伝達制御に関与すると考えられる翻訳後修飾を同定することに成功した。本研究により、自然免疫シグナリングの制御機構に関して新たな仮説を提唱するに至り、その成果は哺乳類自然免疫系の新規制御機構をも示唆する成果である。