RRC ID 18118
Author Watanabe A, Tatematsu M, Saeki K, Shibata S, Shime H, Yoshimura A, Obuse C, Seya T, Matsumoto M.
Title Raftlin is involved in the nucleocapture complex to induce poly(I:C)-mediated TLR3 activation.
Journal J. Biol. Chem.
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.
Volume 286(12)
Pages 10702-11
Published 2011-3-25
DOI 10.1074/jbc.M110.185793
PII M110.185793
PMID 21266579
PMC PMC3060521
MeSH Animals Cell Line, Tumor Cell Membrane / genetics Cell Membrane / metabolism Dendritic Cells / cytology Dendritic Cells / metabolism* Endosomes / genetics Endosomes / metabolism Gene Silencing HEK293 Cells Humans Interferon Inducers / pharmacology* Interferon-beta / biosynthesis Interferon-beta / genetics Membrane Proteins / genetics Membrane Proteins / metabolism* Mice Mice, Knockout Myeloid Cells / cytology Myeloid Cells / metabolism* Poly I-C / pharmacology* Toll-Like Receptor 3 / agonists Toll-Like Receptor 3 / genetics Toll-Like Receptor 3 / metabolism*
IF 4.106
Times Cited 24
Human and Animal Cells Namalwa (RCB0445)