Instituto de Biologia y Genetica Molecular, CSIC-Universidad de Valladolid, Valladolid, Spain.
Cell Death Differ. 2011 Jul;18(7):1161-73. doi: 10.1038/cdd.2010.184. Epub 2011 Jan 21.
Multivesicular bodies (MVBs) are endocytic compartments that contain intraluminal vesicles formed by inward budding from the limiting membrane of endosomes. In T lymphocytes, these vesicles contain pro-apoptotic Fas ligand (FasL), which may be secreted as 'lethal exosomes' upon fusion of MVBs with the plasma membrane. Diacylglycerol kinase α (DGKα) regulate the secretion of exosomes, but it is unclear how this control is mediated. T-lymphocyte activation increases the number of MVBs that contain FasL. DGKα is recruited to MVBs and to exosomes in which it has a double function. DGKα kinase activity exerts a negative role in the formation of mature MVBs, as we demonstrate by the use of an inhibitor. Downmodulation of DGKα protein resulted in inhibition of both the polarisation of MVBs towards immune synapse and exosome secretion. The subcellular location of DGKα together with its complex role in the formation and polarised traffic of MVBs support the notion that DGKα is a key regulator of the polarised secretion of exosomes.
多泡体（MVBs）是内体膜向内出芽形成的含有腔内囊泡的内吞体区室。在 T 淋巴细胞中，这些囊泡含有促凋亡的 Fas 配体（FasL），当 MVB 与质膜融合时，FasL 可能作为“致死性外泌体”被分泌。二酰基甘油激酶α（DGKα）调节外泌体的分泌，但尚不清楚这种调控是如何介导的。T 淋巴细胞的激活增加了含有 FasL 的 MVB 的数量。DGKα 被募集到 MVB 和其中具有双重功能的外泌体。我们通过使用抑制剂证明，DGKα 激酶活性在外泌体成熟 MVB 的形成中发挥负作用。DGKα 蛋白的下调导致 MVB 向免疫突触的极化和外泌体分泌均受到抑制。DGKα 的亚细胞定位及其在 MVB 形成和极化运输中的复杂作用支持 DGKα 是外泌体极化分泌的关键调节剂的观点。
