前沿：UNC93B1 的酪氨酸基基序通过独立的机制调节运输和 TLR 反应。
Cutting edge: the UNC93B1 tyrosine-based motif regulates trafficking and TLR responses via separate mechanisms.
机构信息
Institute of Innate Immunity, University Hospital, University of Bonn, 53127 Bonn, Germany;
Institute of Biochemistry I and Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany;
出版信息
J Immunol. 2014 Oct 1;193(7):3257-61. doi: 10.4049/jimmunol.1301886. Epub 2014 Sep 3.
Sensing of nucleic acids by TLRs is crucial in the host defense against viruses and bacteria. Unc-93 homolog B1 (UNC93B1) regulates the trafficking of nucleic acid-sensing TLRs from the endoplasmic reticulum to endolysosomes, where the TLRs encounter their respective ligands and become activated. In this article, we show that a carboxyl-terminal tyrosine-based sorting motif (YxxΦ) in UNC93B1 differentially regulates human nucleic acid-sensing TLRs in a receptor- and ligand-specific manner. Destruction of YxxΦ abolished TLR7, TLR8, and TLR9 activity toward nucleic acids in human B cells and monocytes, whereas TLR8 responses toward small molecules remained intact. YxxΦ in UNC93B1 influenced the subcellular localization of human UNC93B1 via both adapter protein complex (AP)1- and AP2-dependent trafficking pathways. However, loss of AP function was not causal for altered TLR responses, suggesting AP-independent functions of YxxΦ in UNC93B1.
TLRs 对核酸的感应在宿主防御病毒和细菌方面至关重要。UNC93B1 调节核酸感应 TLR 从内质网到内体溶酶体的运输，在那里 TLR 遇到各自的配体并被激活。在本文中，我们表明 UNC93B1 羧基末端的酪氨酸基分拣基序（YxxΦ）以受体和配体特异性的方式差异调节人类核酸感应 TLR。破坏 YxxΦ 消除了 TLR7、TLR8 和 TLR9 在人 B 细胞和单核细胞中对核酸的活性，而 TLR8 对小分子的反应仍然完整。UNC93B1 中的 YxxΦ 通过衔接蛋白复合物（AP）1 和 AP2 依赖的运输途径影响人 UNC93B1 的亚细胞定位。然而，AP 功能的丧失并不是 TLR 反应改变的原因，这表明 YxxΦ 在 UNC93B1 中具有 AP 独立的功能。
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