Extracellular vesicles are independent metabolic units with asparaginase activity.

Extracellular vesicles are independent metabolic units with asparaginase activity.
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DOI:
10.1038/nchembio.2422
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发表时间:
2017-09
影响因子:
14.8
通讯作者:
Pluchino S
Pluchino S
中科院分区:
生物学1区
文献类型:
--
作者:
Iraci N;Gaude E;Leonardi T;Costa ASH;Cossetti C;Peruzzotti-Jametti L;Bernstock JD;Saini HK;Gelati M;Vescovi AL;Bastos C;Faria N;Occhipinti LG;Enright AJ;Frezza C;Pluchino S

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细胞外囊泡(EV)是参与细胞和微环境之间广泛生物活性分子交换的膜颗粒。虽然已经表明细胞可以通过EV运输代谢酶,但关于其内在的代谢活性仍有待阐明。因此,在本文中,我们评估了神经干/祖细胞(NSC)衍生的EV消耗和产生代谢物的能力。我们的代谢组学和功能分析都显示,EV具有由天冬酰胺酶样蛋白1(Asrgl 1)催化的L-天冬酰胺酶活性。重要的是,我们表明Asrgl 1活性对天冬酰胺具有选择性,并且没有天冬酰胺酶活性。我们发现,小鼠和人类神经干细胞衍生的电动汽车交通ASRGL 1。我们的研究结果首次证明,NSC EV作为独立的细胞外代谢单位发挥作用,能够改变关键营养物质的浓度,并有可能影响其微环境的生理学。
Extracellular vesicles (EVs) are membrane particles involved in the exchange of a broad range of bioactive molecules between cells and the microenvironment. While it has been shown that cells can traffic metabolic enzymes via EVs much remains to be elucidated with regard to their intrinsic metabolic activity. Accordingly, herein we assessed the ability of neural stem/progenitor cell (NSC)-derived EVs to consume and produce metabolites. Both our metabolomics and functional analyses revealed that EVs harbour L-asparaginase activity catalysed by the enzyme Asparaginase-like protein 1 (Asrgl1). Critically, we show that Asrgl1 activity is selective for asparagine and is devoid of glutaminase activity. We found that mouse and human NSC-derived EVs traffic ASRGL1. Our results demonstrate for the first time that NSC EVs function as independent, extracellular metabolic units able to modify the concentrations of critical nutrients, with the potential to affect the physiology of their microenvironment.
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