ALG2 Influences T cell apoptosis by regulating FASLG intracellular transportation
ALG2 Influences T cell apoptosis by regulating FASLG intracellular transportation
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ALG2通过调节FASLG细胞内运输影响T细胞凋亡
DOI：
10.1042/bcj20200028
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发表时间：
2020-08-01
影响因子：
4.1
通讯作者：
Liu, Xinqi
中科院分区：
文献类型：
--
作者：
Ji, Wangsheng;Xin, Yang;Liu, Xinqi
在免疫系统中，T淋巴细胞在病原体感染后经历快速克隆扩增。病原体清除后，大部分增殖的T细胞将通过凋亡途径被清除，以保持免疫细胞的平衡。FASLG通过与其同源受体FAS相互作用，在控制T细胞死亡中起主要作用。FASLG是一种II型跨膜蛋白，其C-末端胞外结构域负责与FAS相互作用。N-末端胞质区域虽然短且本质上是无序的，但对蛋白质的稳定性和转运起着关键作用。FASLG的正确定位，无论是在质膜上或与外泌体一起分泌，还是在蛋白酶切割后脱落到细胞外区域，都对FASLG的正常功能有很大影响。合成后，FASLG通过胞内囊泡转运系统转运至最终目的地。在本报告中，ALG 2，一个在T细胞凋亡中鉴定的分子，以前被证明参与囊泡运输，被发现与FASLG相互作用并调节FASLG的运输。因此，我们确定了一个新的调节因子FASLG功能的T细胞内，也揭示了一个新的途径ALG 2参与T细胞凋亡。
In the immune system, T lymphocytes undergo rapid clonal expansion upon pathogen infection. Following pathogen clearance, most of proliferated T cells will be eliminated by the apoptosis pathway to keep the balance of immune cells. FASLG, by interacting with its cognate receptor FAS, plays a major role in controlling the T cell death. FASLG is a type II transmembrane protein, with its C-terminal extracellular domain responsible for interacting with FAS. The N-terminal cytosolic region, despite short and intrinsically disordered, plays critical roles on the protein stability and transportation. The correct localization, either on the plasma membrane or secreted with exosome, or shed into the extracellular region after protease cleavage, has a great impact on the proper function of FASLG. Following synthesis, FASLG is transported by intracellular vesicle transportation system to the final destination. In this report, ALG2, a molecule identified in the T cell apoptosis and shown to be involved in vesicle trafficking previously, was found to interact with FASLG and regulate FASLG transportation. Therefore, we identified a new regulating factor for FASLG function within T cells and also revealed a new pathway for ALG2 involvement in T cell apoptosis.