RRC ID 54464
Author Itoh H, Tatematsu M, Watanabe A, Iwano K, Funami K, Seya T, Matsumoto M.
Title UNC93B1 physically associates with human TLR8 and regulates TLR8-mediated signaling.
Journal PLoS One
Abstract Toll-like receptors (TLRs) 3, 7, 8, and 9 are localized to intracellular compartments where they encounter foreign or self nucleic acids and activate innate and adaptive immune responses. The endoplasmic reticulum (ER)-resident membrane protein, UNC93B1, is essential for intracellular trafficking and endolysosomal targeting of TLR7 and TLR9. TLR8 is phylogenetically and structurally related to TLR7 and TLR9, but little is known about its localization or function. In this study, we demonstrate that TLR8 localized to the early endosome and the ER but not to the late endosome or lysosome in human monocytes and HeLa transfectants. UNC93B1 physically associated with human TLR8, similar to TLRs 3, 7, and 9, and played a critical role in TLR8-mediated signaling. Localization analyses of TLR8 tail-truncated mutants revealed that the transmembrane domain and the Toll/interleukin-1 receptor domain were required for proper targeting of TLR8 to the early endosome. Hence, although UNC93B1 participates in intracellular trafficking and signaling for all nucleotide-sensing TLRs, the mode of regulation of TLR localization differs for each TLR.
Volume 6(12)
Pages e28500
Published 2011
DOI 10.1371/journal.pone.0028500
PII PONE-D-11-15234
PMID 22164301
PMC PMC3229609
MeSH Endoplasmic Reticulum / metabolism Endosomes / metabolism Flow Cytometry / methods Gene Expression Regulation* HEK293 Cells HeLa Cells Humans Immunity, Innate Lysosomes / metabolism Membrane Transport Proteins / metabolism* Microscopy, Confocal / methods Monocytes / cytology Mutation Phylogeny Plasmids / metabolism RNA Interference Signal Transduction Toll-Like Receptor 8 / metabolism*
IF 2.776
Times Cited 43
Resource
DNA material human TLR8 expression vector (RDB16910) human TLR8-CFlag expression vector (RDB16912)