Mechanism of nucleic acid recognition by endosomal Toll-like receptor 3

内体Toll样受体3识别核酸的机制

• 批准号: 20590483
• 负责人: MATSUMOTO Misako
• 金额: $ 3.08万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590483/
• 关键词: 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

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.

合成的病毒双链RNA类似物poly （I:C）在细胞外激活内体toll样受体（TLR） 3和细胞质RNA解旋酶（黑色素瘤分化相关基因5），导致I型干扰素（ifn）和炎症细胞因子的产生，以及树突状细胞（DC）的成熟。细胞外多聚物（I:C）传递到tlr3阳性细胞器和细胞质的机制尚不清楚。在这项研究中，我们证明了细胞质脂筏蛋白Raftlin对于人类髓系DCs和上皮细胞的聚（I:C）细胞摄取至关重要。当Raftlin被沉默时，poly （I:C）不能进入细胞，诱导IFN-β的产生受到抑制。在poly （I:C）刺激下，Raftlin从细胞质转移到质膜，与poly （I:C）共定位，然后移动到tlr3阳性内体。在响应poly （I:C）的质膜上，Raftlin与网格蛋白物理结合。因此，Raftlin与网格蛋白- ap -2复合物协同介导poly （I:C）进入细胞，这对TLR3的激活至关重要。

项目成果

Raftlin Is Involved in the Nucleocapture Complex to Induce Poly(I:C)-mediated TLR3 Activation

• DOI: 10.1074/jbc.m110.185793
• 发表时间: 2011-03-25
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Watanabe, Ayako;Tatematsu, Megumi;Matsumoto, Misako
• 通讯作者: Matsumoto, Misako

TLR刺激によるTh17細胞の増加

TLR 刺激增加 Th17 细胞

• 发表时间: 2009
• 期刊: 臨床免疫 51(5)
• 作者: 志馬寛明;井上徳光;松本美佐子;瀬谷司
• 通讯作者: 瀬谷司

補体への招待

邀请补充

• 发表时间: 2011
• 作者: Miyazaki;Taisuke ; Yamasaki;Miwako ; Hashimoto;Kouichi;et;松本美佐子,他
• 通讯作者: 松本美佐子,他

アジュバント活性を有する新規核酸およびその利用

具有佐剂活性的新型核酸及其用途

• 发表时间: 2011

Modulation of Double-stranded RNA Recognition by the N-terminal Histidine-rich Region of the Human Toll-like Receptor 3

人 Toll 样受体 3 的 N 末端富含组氨酸区域对双链 RNA 识别的调节

• 发表时间: 2008
• 期刊: J. Biol. Chem. 283
• 作者: Fukuda;K.;T. Watanabe;T. Tokisue;T. Tsujita;S. Nishikawa;T. Hasegawa;T. Seya;M. Matsumoto.
• 通讯作者: M. Matsumoto.