Raftlin is involved in the nucleocapture complex to induce poly(I:C)-mediated TLR3 activation

Ayako Watanabe, Megumi Tatematsu, Kazuko Saeki, Sachiko Shibata, Hiroaki Shime, Akihiko Yoshimura, Chikashi Obuse, Tsukasa Seya, Misako Matsumoto

研究成果: Article査読

58 被引用数 (Scopus)

抄録

The double-stranded RNA analog, 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. The mechanism by which extracellular poly(I:C) is delivered to TLR3-positive organelles and the cytoplasm remains to be elucidated. Here, we show that the cytoplasmic lipid raft protein, Raftlin, is essential for poly(I:C) cellular uptake in human myeloid dendritic cells and epithelial cells. When Raftlin was silenced, poly(I:C) failed to enter cells and induction of IFN-β production was inhibited. In addition, cellular uptake of B-type oligodeoxynucleotide that shares its uptake receptor with poly(I:C) was suppressed in Raftlin knockdown cells. 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. Thus, Raftlin cooperates with the uptake receptor to mediate cell entry of poly(I:C), which is critical for activation of TLR3.

本文言語English
ページ(範囲)10702-10711
ページ数10
ジャーナルJournal of Biological Chemistry
286
12
DOI
出版ステータスPublished - 2011 3月 25

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学

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