| Project/Area Number |
20590483
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | Hokkaido University |
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Principal Investigator |
MATSUMOTO Misako Hokkaido University, 大学院・医学研究科, 准教授 (30332456)
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| Co-Investigator(Renkei-kenkyūsha) |
SEYA Tsukasa 北海道大学, 大学院・医学研究科, 教授 (10301805)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2008: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | 樹状細胞 / Toll-like receptor / 二重鎖RNA / タイプIインターフェロン / ウイルス感染 / エンドソーム / エンドサイトーシス / プロテオーム / 二本鎖RNA / 炎症性サイトカイン / 取り込みレセプター / CDG DNA |
|---|
| Research Abstract |
The synthetic virus double-stranded RNA analogue, poly (I:C), extracellularly activates both the endosomal Toll-like receptor (TLR) 3 and the cytoplasmic RNA helicase, melanoma differentiation-associated gene 5, leading to the production of type I interferons (IFNs) and inflammatory cytokines, and dendritic cell (DC) maturation. The mechanism by which extracellular poly(I:C) is delivered to TLR3-positive organelles and the cytoplasm remains to be elucidated. In this study, we demonstrate that the cytoplasmic lipid raft protein, Raftlin, is essential for poly (I:C) cellular uptake in human myeloid DCs and epithelial cells. When Raftlin was silenced, poly (I:C) failed to enter cells and induction of IFN-β production was inhibited. Upon poly (I:C) stimulation, Raftlin was translocated from the cytoplasm to the plasma membrane where it colocalized with poly (I:C), and thereafter moved to TLR3-positive endosomes. Raftlin physically associated with clathrin at the plasma membrane in response to poly (I:C). Thus, Raftlin cooperates with the clathrin-AP-2 complex to mediate cell entry of poly (I:C), which is critical for activation of TLR3.
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