Extracellular vesicles are independent metabolic units with asparaginase activity.
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Authors
Peruzzotti Jametti, Luca
Saini, Harpreet K
Gelati, Maurizio
Vescovi, Angelo Luigi
Passos Bastos, Carlos
Rodrigues Faria, Nuno
Publication Date
2017-09Journal Title
Nature chemical biology
ISSN
1552-4450
Publisher
Springer Nature
Volume
13
Issue
9
Pages
951-955
Language
English
Type
Article
This Version
AM
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Iraci, N., Gaude, E., Leonardi, T., Costa, A. S., Cossetti, C., Peruzzotti Jametti, L., Bernstock, J., et al. (2017). Extracellular vesicles are independent metabolic units with asparaginase activity.. Nature chemical biology, 13 (9), 951-955. https://doi.org/10.1038/nchembio.2422
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.
Keywords
Asparaginase, Models, Biological, Extracellular Vesicles
Sponsorship
This work has received support from the Italian Multiple Sclerosis Association (AISM, grant 2010/R/31 and grant 2014/PMS/4 to SP), the Italian Ministry of Health (GR08-7 to SP), the European Research Council (ERC) under the ERC-2010-StG Grant agreement n° 260511-SEM_SEM, the Medical Research Council, the Engineering and Physical Sciences Research Council, and the Biotechnology and Biological Sciences Research Council UK Regenerative Medicine Platform Hub “Acellular Approaches for Therapeutic Delivery” (MR/K026682/1 to SP), The Evelyn Trust (RG 69865 to SP), The Bascule Charitable Trust (RG 75149 to SP) and core support grant from the Wellcome Trust and Medical Research Council to the Wellcome Trust – MRC Cambridge Stem Cell Institute. N.I. was supported by a FEBS long-term fellowship. C.F., A.S.H., and E.G. were funded by the Medical Research Council, Core Fund SKAG006.
Funder references
MRC (MC_UU_12022/1_do not transfer?)
EPSRC (EP/K03099X/1)
Medical Research Council (MC_UU_12022/6)
MRC (MC_PC_12009)
MRC (MR/R005699/1)
European Research Council (260511)
Identifiers
External DOI: https://doi.org/10.1038/nchembio.2422
This record's URL: https://www.repository.cam.ac.uk/handle/1810/266573
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