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Nat Chem Biol. 2017 Sep;13(9):951-955. doi: 10.1038/nchembio.2422. Epub 2017 Jul 3.

Extracellular vesicles are independent metabolic units with asparaginase activity.

Author information

1
Wellcome Trust-Medical Research Council Stem Cell Institute, Department of Clinical Neurosciences-Division of Stem Cell Neurobiology, and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
2
MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge Biomedical Campus, Cambridge, UK.
3
European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
4
Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health (NINDS/NIH), Bethesda, Maryland, USA.
5
Stem Cells Laboratory, Cell Factory and Biobank, Azienda Ospedaliera 'Santa Maria', Terni, Italy.
6
IRCCS Casa Sollievo della Sofferenza, Foggia, Italy.
7
Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milano, Italy.
8
Medical Research Council-Elsie Widdowson Laboratory, Cambridge, UK.
9
Department of Engineering, Electrical Engineering Division, University of Cambridge, Cambridge, UK.

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.

PMID:
28671681
PMCID:
PMC5563455
DOI:
10.1038/nchembio.2422
[Indexed for MEDLINE]
Free PMC Article

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