Extracellular vesicles are independent metabolic units with asparaginase activity.

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.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

An evolutionarily stable strategy to colonize spatially extended habitats

The ability of a species to colonize newly available habitats is crucial to its overall fitness1,2,3. In general, motility and fast expansion are expected to be beneficial for colonization and hence for the fitness of an organism4,5,6,7. Here we apply an evolution protocol to investigate phenotypical requirements for colonizing habitats of different sizes during range expansion by chemotaxing bacteria8. Contrary to the intuitive expectation that faster is better, we show that there is an optimal expansion speed for a given habitat size. Our analysis showed that this effect arises from interactions among pioneering cells at the front of the expanding population, and revealed a simple, evolutionarily stable strategy for colonizing a habitat of a specific size: to expand at a speed given by the product of the growth rate and the habitat size. These results illustrate stability-to-invasion as a powerful principle for the selection of phenotypes in complex ecological processes