Rab6 regulates recycling and retrograde trafficking of MR1 molecules.
Rab6 regulates recycling and retrograde trafficking of MR1 molecules.
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Rab6调节MR1分子的再循环和逆行运输。
DOI：
10.1038/s41598-020-77563-4
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发表时间：
2020-11-27
影响因子：
4.6
通讯作者：
Harriff MJ
中科院分区：
文献类型：
--
作者：
Huber ME;Kurapova R;Heisler CM;Karamooz E;Tafesse FG;Harriff MJ
粘膜相关不变性T细胞（MAIT）是一种先天样T细胞亚群，在对细菌和病毒性肺病原体的早期反应中起重要作用。MAIT细胞识别i类分子MR1上呈现的细菌小分子代谢物。与其他I类和II类分子一样，MR1可能通过多种细胞途径在细胞内环境中取样配体。Rab6是一种小的GTPase，它调节许多内体运输途径，包括逆行运输到反式高尔基网络（TGN），参与了从结核分枝杆菌（Mtb）到MAIT细胞的配体的呈现。rab6介导的转运途径包含与结核分枝杆菌细胞内腔室共享特征的内体腔室。利用MR1的诱导表达，本研究表明Rab6调节MR1分子从细胞表面通过内体转运室到TGN的再循环。这种依赖于rab6的循环MR1库可用于重新装载来自结核分枝杆菌等细菌病原体的配体，可能对肺部MAIT细胞早期识别感染细胞很重要。
Mucosal-associated invariant T (MAIT) cells are an innate-like T cell subset important in the early response to bacterial and viral lung pathogens. MAIT cells recognize bacterial small molecule metabolites presented on the Class I-like molecule MR1. As with other Class I and Class II molecules, MR1 can likely sample ligands in the intracellular environment through multiple cellular pathways. Rab6, a small GTPase that regulates a number of endosomal trafficking pathways including retrograde transport to the trans-Golgi network (TGN), is involved in the presentation of ligands from Mycobacterium tuberculosis (Mtb) to MAIT cells. The Rab6-mediated trafficking pathway contains endosomal compartments that share features with the Mtb intracellular compartment. Using inducible expression of MR1, this study demonstrates that Rab6 regulates the recycling of MR1 molecules from the cell surface through endosomal trafficking compartments to the TGN. This Rab6-dependent pool of recycled MR1, which is available for reloading with ligands from bacterial pathogens like Mtb, may be important for early recognition of infected cells by MAIT cells in the lung.
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