A protein associated with toll-like receptor 4 (PRAT4A) regulates cell surface expression of TLR4
A protein associated with toll-like receptor 4 (PRAT4A) regulates cell surface expression of TLR4
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DOI：
10.4049/jimmunol.177.3.1772
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发表时间：
2006-08-01
影响因子：
4.4
通讯作者：
Miyake, Kensuke
中科院分区：
文献类型：
--
作者：
Wakabayashi, Yasutaka;Kobayashi, Makiko;Miyake, Kensuke
TLR识别微生物产物。它们的亚细胞分布被优化用于微生物识别。然而，关于调节TLR亚细胞分布的机制知之甚少。LPS被由TLR 4和MD-2组成的受体复合物识别。虽然MD-2，TLR 4的辅助受体，增强TLR 4的细胞表面表达，调节TLR 4分布的另一种机制已被提出。我们在这里显示，PRAT 4A，一种新的蛋白质与TLR 4，调节TLR 4的细胞表面表达。PRAT 4A与TLR 4的未成熟形式相关，但与MD-2或TLR 2无关。PRAT 4A敲低消除了表达TLR 4/MD-2的细胞系中的LPS反应性，这可能是由于缺乏细胞表面TLR 4。PRAT 4A敲低下调树突状细胞上的细胞表面TLR 4/MD-2。这些结果证明了调节细胞表面TLR 4/MD-2表达的新机制。
TLRs recognize microbial products. Their subcellular distribution is optimized for microbial recognition. Little is known,,however, about mechanisms regulating the subcellular distribution of TLRs. LPS is recognized by the receptor complex consisting of TLR4 and MD-2. Although MD-2, a coreceptor for TLR4, enhances cell surface expression of TLR4, an additional mechanism regulating TLR4 distribution has been suggested. We show here that PRAT4A, a novel protein associated with TLR4, regulates cell surface expression of TLR4. PRAT4A is associated with the immature form of TLR4 but not with MD-2 or TLR2. PRAT4A knockdown abolished LPS responsiveness in a cell line expressing TLR4/MD-2, probably due to the lack of cell surface TLR4. PRAT4A knockdown down-regulated cell surface TLR4/MD-2 on dendritic cells. These results demonstrate a novel mechanism regulating TLR4/MD-2 expression on the cell surface.