The role of novel molecules on innate immune respose.

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K15731
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Kumamoto University
• Principal Investigator: Kouwaki Takahisa 熊本大学, 大学院生命科学研究部(医), 助教 (90780784)
• Research Collaborator: Oshiumi Hiroyuki
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 自然免疫 / RIG-I / MAVS / Zyxin

Outline of Final Research Achievements

RIG-I-like receptors (RLRs) are cytoplasmic viral RNA sensors, which induce antiviral innate immune responses. After recognition of viral RNA, RLRs bind to the MAVS adaptor molecule, resulting in downstream signaling. To reveal the molecular mechanism of MAVS-dependent signaling, we performed a yeast two-hybrid screening and identified zyxin as a protein that binds to MAVS. Zyxin interacted with MAVS in human cells. A proximity ligation assay showed that zyxin and MAVS partly co-localized on mitochondria. Ectopic expression of zyxin augmented MAVS-mediated IFN-β promoter activation, and knockdown of zyxin (ZYX) attenuated the IFN-β promoter activation. Moreover, ZYX knockdown reduced the expression of type I IFN and an interferon-inducible gene after stimulation with ligands of RLRs. Interestingly, physical interactions between RLRs and MAVS were abrogated by ZYX knockdown. These observations indicate that zyxin serves as a scaffold for the interactions between RLRs and MAVS.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

ウイルスRNAセンサーによるインターフェロン誘導は宿主のタンパク質によって厳密に制御されている。RLRsはウイルスを認識すると、MAVSが存在するミトコンドリアまで移動することが知られている。本研究で我々は、RLRsとMAVSの相互作用の足場としてZyxinが役割を果たしていることを発見した。この発見はウイルス感染が誘導する抗ウイルス応答を制御する新たなメカニズムを提唱できたいう面で意義深い。