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Extracellular vesicles are independent metabolic units with asparaginase activity.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Gaude, Edoardo 
Leonardi, Tommaso 
Costa, Ana SH 
Cossetti, Chiara 

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.

Description

Keywords

Asparaginase, Extracellular Vesicles, Models, Biological

Journal Title

Nat Chem Biol

Conference Name

Journal ISSN

1552-4450
1552-4469

Volume Title

13

Publisher

Springer Science and Business Media LLC
Sponsorship
MRC (unknown)
Engineering and Physical Sciences Research Council (EP/K03099X/1)
Medical Research Council (MC_UU_12022/6)
Medical Research Council (MC_PC_12009)
Medical Research Council (MR/R005699/1)
European Research Council (260511)
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.