UNC93B1 Physically Associates with Human TLR8 and Regulates TLR8-Mediated Signaling

PLoS One

Tsukasa Seya¹  Hiroki Itoh¹  Katsunori Iwano¹  Misako Matsumoto¹  Megumi Tatematsu¹  Ayako Watanabe¹  Kenji Funami¹ 

[1] Department of Microbiology and Immunology, Hokkaido University Graduate School of Medicine, Sapporo, Japan

关键词: Toll-like receptors;    Immune receptor signaling;    Endosomes;    Membrane receptor signaling;    Monocytes;    Plasmid construction;    DAPI staining;    Transcription factors;   

DOI  :  10.1371/journal.pone.0028500

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY