UNC93B1 mediates differential trafficking of endosomal TLRs
UNC93B1 mediates differential trafficking of endosomal TLRs
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DOI：
10.1155/2013/961957
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发表时间：
2013-02-19
期刊：
影响因子：
7.7
通讯作者：
Barton, Gregory M.
中科院分区：
文献类型：
--
作者：
Lee, Bettina L.;Moon, Joanne E.;Barton, Gregory M.
UNC 93 B1是TLR 3、TLR 7、TLR 9、TLR 11、TLR 12和TLR 13功能所需的多通道跨膜蛋白，控制TLR从内质网（ER）向内溶酶体的运输。UNC 93 B1介导这些调节作用的机制尚不清楚。在这里，我们证明，UNC 93 B1进入分泌途径，并直接控制包装的TLR进入COPII囊泡，芽从ER。与其他COPII加载因子不同，UNC 93 B1通过后高尔基体分选步骤保持与TLR相关。出乎意料的是，这些步骤在内体TLR中是不同的。TLR 9需要UNC 93 B1介导的衔接蛋白复合物2（AP-2）的募集以递送至内溶酶体，而TLR 7、TLR 11、TLR 12和TLR 13利用替代运输途径。因此，我们的研究描述了UNC 93 B1对内体TLR进行差异分选的机制，这可能解释了这些受体在某些自身免疫性疾病中所起的不同作用。
UNC93B1, a multipass transmembrane protein required for TLR3, TLR7, TLR9, TLR11, TLR12, and TLR13 function, controls trafficking of TLRs from the endoplasmic reticulum (ER) to endolysosomes. The mechanisms by which UNC93B1 mediates these regulatory effects remain unclear. Here, we demonstrate that UNC93B1 enters the secretory pathway and directly controls the packaging of TLRs into COPII vesicles that bud from the ER. Unlike other COPII loading factors, UNC93B1 remains associated with the TLRs through post-Golgi sorting steps. Unexpectedly, these steps are different among endosomal TLRs. TLR9 requires UNC93B1-mediated recruitment of adaptor protein complex 2 (AP-2) for delivery to endolysosomes while TLR7, TLR11, TLR12, and TLR13 utilize alternative trafficking pathways. Thus, our study describes a mechanism for differential sorting of endosomal TLRs by UNC93B1, which may explain the distinct roles played by these receptors in certain autoimmune diseases.