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标题：Exosomes account for vesicle-mediated transcellular transport of activatable phospholipases and prostaglandins
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作者：Caroline Subra ; David Grand ; Karine Laulagnier 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2010
卷号：51
期号：8
页码：2105-2120
DOI：10.1194/jlr.M003657
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Exosomes are bioactive vesicles released from multivesicular bodies (MVB) by intact cells and participate in intercellular signaling. We investigated the presence of lipid-related proteins and bioactive lipids in RBL-2H3 exosomes. Besides a phospholipid scramblase and a fatty acid binding protein, the exosomes contained the whole set of phospholipases (A2, C, and D) together with interacting proteins such as aldolase A and Hsp 70. They also contained the phospholipase D (PLD) / phosphatidate phosphatase 1 (PAP1) pathway leading to the formation of diglycerides. RBL-2H3 exosomes also carried members of the three phospholipase A2 classes: the calcium-dependent cPLA₂-IVA, the calcium-independent iPLA₂-VIA, and the secreted sPLA₂-IIA and V. Remarkably, almost all members of the Ras GTPase superfamily were present, and incubation of exosomes with GTPγS triggered activation of phospholipase A₂ (PLA₂)and PLD₂. A large panel of free fatty acids, including arachidonic acid (AA) and derivatives such as prostaglandin E₂ (PGE₂) and 15-deoxy-Δ^12,14-prostaglandinJ₂ (15-d PGJ₂), were detected. We observed that the exosomes were internalized by resting and activated RBL cells and that they accumulated in an endosomal compartment. Endosomal concentrations were in the micromolar range for prostaglandins; i.e., concentrations able to trigger prostaglandin-dependent biological responses. Therefore exosomes are carriers of GTP-activatable phospholipases and lipid mediators from cell to cell.
关键词：exosome ; phosphatidate phosphatase ; arachidonic acid ; docosahexaenoic acid ; prostaglandin