Extracellular vesicles are independent metabolic units with asparaginase activity

Nunzio Iraci; Edoardo Gaude; Tommaso Leonardi; Ana S.H. Costa; Chiara Cossetti; Luca Peruzzotti-Jametti; Joshua D. Bernstock; Harpreet K. Saini; Maurizio Gelati; Angelo Luigi Vescovi; Carlos Bastos; Nuno Faria; Luigi G. Occhipinti; Anton J. Enright; Christian Frezza; Stefano Pluchino

doi:10.1038/nchembio.2422

Extracellular vesicles are independent metabolic units with asparaginase activity

Nunzio Iraci, Edoardo Gaude, Tommaso Leonardi, Ana S.H. Costa, Chiara Cossetti, Luca Peruzzotti-Jametti, Joshua D. Bernstock, Harpreet K. Saini, Maurizio Gelati, Angelo Luigi Vescovi, Carlos Bastos, Nuno Faria, Luigi G. Occhipinti, Anton J. Enright, Christian Frezza, Stefano Pluchino

Academic Institute

Research output: Contribution to journal › Article › peer-review

108 Scopus citations

Abstract

Extracellular vesicles (EVs) are membrane particles involved in the exchange of a broad range of bioactive molecules between cells and the microenvironment. Although 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. Our metabolomics and functional analyses both revealed that EVs harbor L-asparaginase activity, catalyzed 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 EVs traffic Asrgl1. Our results demonstrate, for the first time, that NSC EVs function as independent metabolic units that are able to modify the concentrations of critical nutrients, with the potential to affect the physiology of their microenvironment.

Original language	English (US)
Pages (from-to)	951-955
Number of pages	5
Journal	Nature Chemical Biology
Volume	13
Issue number	9
DOIs	https://doi.org/10.1038/nchembio.2422
State	Published - Sep 1 2017

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1038/nchembio.2422

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Iraci, N., Gaude, E., Leonardi, T., Costa, A. S. H., Cossetti, C., Peruzzotti-Jametti, L., Bernstock, J. D., Saini, H. K., Gelati, M., Vescovi, A. L., Bastos, C., Faria, N., Occhipinti, L. G., Enright, A. J., Frezza, C., & Pluchino, S. (2017). Extracellular vesicles are independent metabolic units with asparaginase activity. Nature Chemical Biology, 13(9), 951-955. https://doi.org/10.1038/nchembio.2422

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 2017, 'Extracellular vesicles are independent metabolic units with asparaginase activity', Nature Chemical Biology, vol. 13, no. 9, pp. 951-955. https://doi.org/10.1038/nchembio.2422

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abstract = "Extracellular vesicles (EVs) are membrane particles involved in the exchange of a broad range of bioactive molecules between cells and the microenvironment. Although 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. Our metabolomics and functional analyses both revealed that EVs harbor L-asparaginase activity, catalyzed 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 EVs traffic Asrgl1. Our results demonstrate, for the first time, that NSC EVs function as independent metabolic units that are able to modify the concentrations of critical nutrients, with the potential to affect the physiology of their microenvironment.",

author = "Nunzio Iraci and Edoardo Gaude and Tommaso Leonardi and Costa, {Ana S.H.} and Chiara Cossetti and Luca Peruzzotti-Jametti and Bernstock, {Joshua D.} and Saini, {Harpreet K.} and Maurizio Gelati and Vescovi, {Angelo Luigi} and Carlos Bastos and Nuno Faria and Occhipinti, {Luigi G.} and Enright, {Anton J.} and Christian Frezza and Stefano Pluchino",

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AU - Gaude, Edoardo

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AU - Peruzzotti-Jametti, Luca

AU - Bernstock, Joshua D.

AU - Saini, Harpreet K.

AU - Gelati, Maurizio

AU - Vescovi, Angelo Luigi

AU - Bastos, Carlos

AU - Faria, Nuno

AU - Occhipinti, Luigi G.

AU - Enright, Anton J.

AU - Frezza, Christian

AU - Pluchino, Stefano

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Extracellular vesicles are independent metabolic units with asparaginase activity

Abstract

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