UNC93B1 physically associates with human TLR8 and regulates TLR8-mediated signaling.
UNC93B1 physically associates with human TLR8 and regulates TLR8-mediated signaling.
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DOI：
10.1371/journal.pone.0028500
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Matsumoto M
中科院分区：
文献类型：
--
作者：
Itoh H;Tatematsu M;Watanabe A;Iwano K;Funami K;Seya T;Matsumoto M
Toll样受体（TLR）3、7、8和9定位于细胞内区室，在那里它们遇到外来或自身核酸并激活先天性和适应性免疫应答。内质网（ER）驻留膜蛋白，UNC 93 B1，是细胞内运输和TLR 7和TLR 9的内溶酶体靶向所必需的。TLR 8与TLR 7和TLR 9在遗传和结构上相关，但对其定位或功能知之甚少。在这项研究中，我们证明，TLR 8定位于早期内体和ER，但不晚内体或溶酶体在人单核细胞和HeLa转染。UNC 93 B1与人TLR 8（类似于TLR 3、7和9）物理相关，并在TLR 8介导的信号传导中发挥关键作用。TLR 8尾部截短突变体的定位分析表明，跨膜结构域和Toll/白细胞介素-1受体结构域是TLR 8正确靶向早期内体所必需的。因此，尽管UNC 93 B1参与所有核苷酸敏感TLR的细胞内运输和信号传导，但TLR定位的调节模式对于每种TLR不同。
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.
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DOI：
10.1084/jem.20091573
发表时间：
2010-11-22
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ebihara T;Azuma M;Oshiumi H;Kasamatsu J;Iwabuchi K;Matsumoto K;Saito H;Taniguchi T;Matsumoto M;Seya T
通讯作者：
Seya T
影响因子：
4.4
作者：
Muzio, M;Bosisio, D;Mantovani, A
通讯作者：
Mantovani, A
影响因子：
4.4
作者：
Funami, K;Matsumoto, M;Seya, T
通讯作者：
Seya, T
影响因子：
64.5
作者：
通讯作者：
--
DOI：
10.1084/jem.20092140
发表时间：
2010-06-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Jongbloed SL;Kassianos AJ;McDonald KJ;Clark GJ;Ju X;Angel CE;Chen CJ;Dunbar PR;Wadley RB;Jeet V;Vulink AJ;Hart DN;Radford KJ
通讯作者：
Radford KJ