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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)10702-10711
Number of pages10
JournalJournal of Biological Chemistry
Volume286
Issue number12
DOIs
Publication statusPublished - 2011 Mar 25

Fingerprint

Poly I-C
Chemical activation
Cytoplasm
Toll-Like Receptor 3
RNA Helicases
Interferon Type I
Double-Stranded RNA
polyriboinosinic-polyribocytidylic acid
Oligodeoxyribonucleotides
Endosomes
Myeloid Cells
Cell membranes
Organelles
Dendritic Cells
Interferons
Melanoma
Genes
Epithelial Cells
Cell Membrane
Cytokines

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Raftlin is involved in the nucleocapture complex to induce poly(I : C)-mediated TLR3 activation. / Watanabe, Ayako; Tatematsu, Megumi; Saeki, Kazuko; Shibata, Sachiko; Shime, Hiroaki; Yoshimura, Akihiko; Obuse, Chikashi; Seya, Tsukasa; Matsumoto, Misako.

In: Journal of Biological Chemistry, Vol. 286, No. 12, 25.03.2011, p. 10702-10711.

Research output: Contribution to journalArticle

Watanabe, A, Tatematsu, M, Saeki, K, Shibata, S, Shime, H, Yoshimura, A, Obuse, C, Seya, T & Matsumoto, M 2011, 'Raftlin is involved in the nucleocapture complex to induce poly(I: C)-mediated TLR3 activation', Journal of Biological Chemistry, vol. 286, no. 12, pp. 10702-10711. https://doi.org/10.1074/jbc.M110.185793
Watanabe, Ayako ; Tatematsu, Megumi ; Saeki, Kazuko ; Shibata, Sachiko ; Shime, Hiroaki ; Yoshimura, Akihiko ; Obuse, Chikashi ; Seya, Tsukasa ; Matsumoto, Misako. / Raftlin is involved in the nucleocapture complex to induce poly(I : C)-mediated TLR3 activation. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 12. pp. 10702-10711.
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