Regulation of exosome release by glycosphingolipids and flotillins
Regulation of exosome release by glycosphingolipids and flotillins
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DOI：
10.1111/febs.12775
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发表时间：
2014-05-01
期刊：
影响因子：
5.4
通讯作者：
Llorente, Alicia
中科院分区：
文献类型：
--
作者：
Phuyal, Santosh;Hessvik, Nina P.;Llorente, Alicia
外泌体在多泡体与质膜融合后由细胞释放。这一过程的分子机制尚不清楚。我们研究了鞘脂和flotillins的作用，这构成了一个筏相关的蛋白质家族，在释放外泌体。有趣的是，我们的结果表明，dl-苏型-1-苯基-2-癸酰氨基-3-吗啉代-1-丙醇，葡萄糖神经酰胺合酶的抑制剂，似乎影响从PC-3细胞释放的外泌体的组成。然而，伏马菌素B（1）抑制神经酰胺从从头途径的形成并不影响外泌体的分泌。此外，与迄今为止发表的其他细胞系获得的结果相反，抑制中性鞘磷脂酶2（一种催化鞘磷脂形成神经酰胺的酶）不会抑制PC-3细胞中外泌体的分泌。最后，小干扰RNA介导的flotillin-1和flotillin-2的下调并没有显著改变释放的外泌体的水平，但似乎影响了外泌体的组成。总之，我们的研究结果揭示了鞘糖脂和漂浮蛋白参与PC-3细胞外泌体的释放，并表明神经酰胺在外泌体形成中的作用可能是细胞依赖性的。
Exosomes are released by cells after fusion of multivesicular bodies with the plasma membrane. The molecular mechanism of this process is still unclear. We investigated the role of sphingolipids and flotillins, which constitute a raft-associated family of proteins, in the release of exosomes. Interestingly, our results show that dl-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, an inhibitor of glucosylceramide synthase, seemed to affect the composition of exosomes released from PC-3 cells. However, the inhibition of ceramide formation from the denovo pathway by fumonisinB(1) did not affect exosome secretion. Moreover, in contrast to findings obtained with other cell lines published so far, inhibition of neutral sphingomyelinase2, an enzyme that catalyzes the formation of ceramide from sphingomyelin, did not inhibit the secretion of exosomes in PC-3 cells. Finally, small interfering RNA-mediated downregulation of flotillin-1 and flotillin-2 did not significantly change the levels of released exosomes as such, but seemed to affect the composition of exosomes. In conclusion, our results reveal the involvement of glycosphingolipids and flotillins in the release of exosomes from PC-3 cells, and indicate that the role of ceramide in exosome formation may be cell-dependent.