Journal
NATURE CHEMICAL BIOLOGY
Volume 13, Issue 9, Pages 951-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/NCHEMBIO.2422
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Funding
- Italian Multiple Sclerosis Association (AISM) [2010/R/31, 2014/PMS/4]
- Italian Ministry of Health [GR08-7]
- European Research Council (ERC) [260511-SEM_SEM]
- Medical Research Council [SKAG006]
- Engineering and Physical Sciences Research Council
- Biotechnology and Biological Sciences Research Council UK Regenerative Medicine Platform Hub Acellular Approaches for Therapeutic Delivery [MR/K026682/1]
- Evelyn Trust [69865]
- Bascule Charitable Trust [RG 75149]
- Wellcome Trust
- FEBS long-term fellowship
- Engineering and Physical Sciences Research Council [EP/K03099X/1] Funding Source: researchfish
- Medical Research Council [MC_UU_12022/6, MR/R005699/1, MR/K026682/1, MC_PC_12009] Funding Source: researchfish
- EPSRC [EP/K03099X/1] Funding Source: UKRI
- MRC [MC_UU_12022/6, MR/K026682/1, MR/R005699/1] Funding Source: UKRI
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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.
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