| First Author | Watanabe A | Year | 2011 |
| Journal | J Biol Chem | Volume | 286 |
| Issue | 12 | Pages | 10702-11 |
| PubMed ID | 21266579 | Mgi Jnum | J:170947 |
| Mgi Id | MGI:4947923 | Doi | 10.1074/jbc.M110.185793 |
| Citation | Watanabe A, et al. (2011) Raftlin Is Involved in the Nucleocapture Complex to Induce Poly(I:C)-mediated TLR3 Activation. J Biol Chem 286(12):10702-11 |
| abstractText | 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-beta 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. |
