Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Active endocannabinoids are secreted on extracellular membrane vesicles.

ABSTRACT: Endocannabinoids primarily influence neuronal synaptic communication within the nervous system. To exert their function, endocannabinoids need to travel across the intercellular space. However, how hydrophobic endocannabinoids cross cell membranes and move extracellularly remains an unresolved problem. Here, we show that endocannabinoids are secreted through extracellular membrane vesicles produced by microglial cells. We demonstrate that microglial extracellular vesicles carry on their surface N-arachidonoylethanolamine (AEA), which is able to stimulate type-1 cannabinoid receptors (CB1), and inhibit presynaptic transmission, in target GABAergic neurons. This is the first demonstration of a functional role of extracellular vesicular transport of endocannabinoids.

SUBMITTER: Gabrielli M

PROVIDER: S-EPMC4328748 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Active endocannabinoids are secreted on extracellular membrane vesicles.

Gabrielli Martina M Battista Natalia N Riganti Loredana L Prada Ilaria I Antonucci Flavia F Cantone Laura L Matteoli Michela M Maccarrone Mauro M Verderio Claudia C

EMBO reports 20150107 2

Endocannabinoids primarily influence neuronal synaptic communication within the nervous system. To exert their function, endocannabinoids need to travel across the intercellular space. However, how hydrophobic endocannabinoids cross cell membranes and move extracellularly remains an unresolved problem. Here, we show that endocannabinoids are secreted through extracellular membrane vesicles produced by microglial cells. We demonstrate that microglial extracellular vesicles carry on their surface ...[more]

PMID: 25568329

Similar Datasets

Listeria monocytogenes virulence factors, including listeriolysin O, are secreted in biologically active extracellular vesicles.

Project description:Outer membrane vesicles produced by Gram-negative bacteria have been studied for half a century but the possibility that Gram-positive bacteria secrete extracellular vesicles (EVs) was not pursued until recently due to the assumption that the thick peptidoglycan cell wall would prevent their release to the environment. However, following their discovery in fungi, which also have cell walls, EVs have now been described for a variety of Gram-positive bacteria. EVs purified from Gram-positive bacteria are implicated in virulence, toxin release, and transference to host cells, eliciting immune responses, and spread of antibiotic resistance. Listeria monocytogenes is a Gram-positive bacterium that causes listeriosis. Here we report that L. monocytogenes produces EVs with diameters ranging from 20 to 200 nm, containing the pore-forming toxin listeriolysin O (LLO) and phosphatidylinositol-specific phospholipase C (PI-PLC). Cell-free EV preparations were toxic to mammalian cells, the murine macrophage cell line J774.16, in a LLO-dependent manner, evidencing EV biological activity. The deletion of plcA increased EV toxicity, suggesting PI-PLC reduced LLO activity. Using simultaneous metabolite, protein, and lipid extraction (MPLEx) multiomics we characterized protein, lipid, and metabolite composition of bacterial cells and secreted EVs and found that EVs carry the majority of listerial virulence proteins. Using immunogold EM we detected LLO at several organelles within infected human epithelial cells and with high-resolution fluorescence imaging we show that dynamic lipid structures are released from L. monocytogenes during infection. Our findings demonstrate that L. monocytogenes uses EVs for toxin release and implicate these structures in mammalian cytotoxicity.

| S-EPMC6349127 | biostudies-literature

Extracellular vesicles released by microglia and macrophages carry endocannabinoids which foster oligodendrocyte differentiation.

Project description:IntroductionMicroglia and macrophages can influence the evolution of myelin lesions through the production of extracellular vesicles (EVs). While microglial EVs promote in vitro differentiation of oligodendrocyte precursor cells (OPCs), whether EVs derived from macrophages aid or limit OPC maturation is unknown.MethodsImmunofluorescence analysis for the myelin protein MBP was employed to evaluate the impact of EVs from primary rat macrophages on cultured OPC differentiation. Raman spectroscopy and liquid chromatography-mass spectrometry was used to define the promyelinating lipid components of myelin EVs obtained in vitro and isolated from human plasma.Results and discussionHere we show that macrophage-derived EVs do not promote OPC differentiation, and those released from macrophages polarized towards an inflammatory state inhibit OPC maturation. However, their lipid cargo promotes OPC maturation in a similar manner to microglial EVs. We identify the promyelinating endocannabinoids anandamide and 2-arachidonoylglycerol in EVs released by both macrophages and microglia in vitro and circulating in human plasma. Analysis of OPC differentiation in the presence of the endocannabinoid receptor antagonists SR141716A and AM630 reveals a key role of vesicular endocannabinoids in OPC maturation. From this study, EV-associated endocannabinoids emerge as important mediators in microglia/macrophage-oligodendrocyte crosstalk, which may be exploited to enhance myelin repair.

| S-EPMC10921360 | biostudies-literature

Membrane Active Peptides Remove Surface Adsorbed Protein Corona From Extracellular Vesicles of Red Blood Cells.

Project description:Besides the outstanding potential in biomedical applications, extracellular vesicles (EVs) are also promising candidates to expand our knowledge on interactions between vesicular surface proteins and small-molecules which exert biomembrane-related functions. Here we provide mechanistic details on interactions between membrane active peptides with antimicrobial effect (MAPs) and red blood cell derived EVs (REVs) and we demonstrate that they have the capacity to remove members of the protein corona from REVs even at lower than 5 ?M concentrations. In case of REVs, the Soret-band arising from the membrane associated hemoglobins allowed to follow the detachment process by flow-Linear Dichroism (flow-LD). Further on, the significant change on the vesicle surfaces was confirmed by transmission electron microscopy (TEM). Since membrane active peptides, such as melittin have the affinity to disrupt vesicles, a combination of techniques, fluorescent antibody labeling, microfluidic resistive pulse sensing, and flow-LD were employed to distinguish between membrane destruction and surface protein detachment. The removal of protein corona members is a newly identified role for the investigated peptides, which indicates complexity of their in vivo function, but may also be exploited in synthetic and natural nanoparticle engineering. Furthermore, results also promote that EVs can be used as improved model systems for biophysical studies providing insight to areas with so far limited knowledge.

| S-EPMC7432246 | biostudies-literature

Extracellular Vesicles Secreted by Corneal Epithelial Cells Promote Myofibroblast Differentiation.

Project description:The corneal epithelium mediates the initial response to injury of the ocular surface and secretes a number of profibrotic factors that promote corneal scar development within the stroma. Previous studies have shown that corneal epithelial cells also secrete small extracellular vesicles (EVs) in response to corneal wounding. In this paper, we hypothesized that EVs released from corneal epithelial cells in vitro contain protein cargo that promotes myofibroblast differentiation, the key cell responsible for scar development. We focused on the interplay between corneal epithelial-derived EVs and the stroma to determine if the corneal fibroblast phenotype, contraction, proliferation, or migration were promoted following vesicle uptake by corneal fibroblasts. Our results showed an increase in myofibroblast differentiation based on α-smooth muscle actin expression and elevated contractility following EV treatment compared to controls. Furthermore, we characterized the contents of epithelial cell-derived EVs using proteomic analysis and identified the presence of provisional matrix proteins, fibronectin and thrombospondin-1, as the dominant encapsulated protein cargo secreted by corneal epithelial cells in vitro. Proteins associated with the regulation of protein translation were also abundant in EVs. This paper reveals a novel role and function of EVs secreted by the corneal epithelium that may contribute to corneal scarring.

| S-EPMC7290736 | biostudies-literature

mRNA data from extracellular vesicles secreted by Trichuris muris

Project description:RNA-Seq analysis of the mRNA present in the extracellular vesicles secreted by the nematode Trichuris muris

2017-12-13 | GSE107986 | GEO

miRNA data from extracellular vesicles secreted by Trichuris muris

Project description:miRNA-Seq analysis of the miRNA present in the extracellular vesicles secreted by the nematode Trichuris muris

2017-12-13 | GSE107985 | GEO

miRNA data from extracellular vesicles secreted by Nippostrongylus brasiliensis

Project description:miRNA-Seq analysis of the miRNA present in the extracellular vesicles secreted by the nematode Nippostrongylus brasiliensis

2018-04-01 | GSE111478 | GEO

Extracellular Vesicles Secreted by Hypoxic AC10 Cardiomyocytes Modulate Fibroblast Cell Motility.

Project description:Extracellular vesicles (EVs) are small membrane vesicles secreted by most cell types with important roles in cell-to-cell communication. To assess their relevance in the context of heart ischemia, EVs isolated from the AC10 ventricular cardiomyocyte cell line (CM-EVs), exposed to normoxia (Nx) or hypoxia (Hx), were incubated with fibroblasts (Fb) and endothelial cells (EC). CM-EVs were studied using electron microscopy, nanoparticle tracking analysis (NTA), western blotting and proteomic analysis. Results showed that EVs had a strong preference to be internalized by EC over fibroblasts, suggesting an active exosome-based communication mechanism between CM and EC in the heart. In Matrigel tube-formation assays, Hx CM-EVs were inferior to Nx CM-EVs in angiogenesis. By contrast, in a wound-healing assay, wound closure was faster in fibroblasts treated with Hx CM-EVs than with Nx CM-EVs, supporting a pro-fibrotic effect of Hx CM-EVs. Overall, these observations were consistent with the different protein cargoes detected by proteomic analysis under Nx and Hx conditions and the biological pathways identified. The paracrine crosstalk between CM-EVs, Fb, and EC in different physiological conditions could account for the contribution of CM-EVs to cardiac remodeling after an ischemic insult.

| S-EPMC6209632 | biostudies-literature

Characterization of Extracellular Vesicles Secreted in Lentiviral Producing HEK293SF Cell Cultures.

Project description:Lentiviral vectors (LVs) are a powerful tool for gene and cell therapy and human embryonic kidney cells (HEK293) have been extensively used as a platform for production of these vectors. Like most cells and cellular tissues, HEK293 cells release extracellular vesicles (EVs). EVs released by cells share similar size, biophysical characteristics and even a biogenesis pathway with cell-produced enveloped viruses, making it a challenge to efficiently separate EVs from LVs. Thus, EVs co-purified with LVs during downstream processing, are considered "impurities" in the context of gene and cell therapy. A greater understanding of EVs co-purifying with LVs is needed to enable improved downstream processing. To that end, EVs from an inducible lentivirus producing cell line were studied under two conditions: non-induced and induced. EVs were identified in both conditions, with their presence confirmed by transmission electron microscopy and Western blot. EV cargos from each condition were then further characterized by a multi-omic approach. Nineteen proteins were identified by mass spectrometry as potential EV markers to differentiate EVs in LV preparations. Lipid composition of EV preparations before and after LV induction showed similar enrichment in phosphatidylserine. RNA cargos in EVs showed enrichment in transcripts involved in viral processes and binding functions. These findings provide insights on the product profile of lentiviral preparations and could support the development of improved separation strategies aimed at removing co-produced EVs.

| S-EPMC8145507 | biostudies-literature

Organ-Specific Uptake of Extracellular Vesicles Secreted by Urological Cancer Cells.

Project description:Extracellular vesicles (EVs) secreted by cancer cells have been shown to take a pivotal part in the process of local and systemic tumor progression by promoting the formation of a supportive local tumor microenvironment and preparing premetastatic niches in distant organ systems. In this study, we analyzed the organ-specific uptake of EVs secreted by urological cancer cells using an innovative in-vivo approach. EVs from benign and malignant prostate, kidney, and bladder cells were isolated using ultracentrifugation, fluorescence-labeled and injected intravenously in immunodeficient mice. After 12 or 24 h, the animals were sacrificed, their organs were harvested and analyzed for the presence of EVs by high-resolution fluorescence microscopy. Across all entities, EVs were taken up fast (12 h > 24 h), and EVs from malignant cells were taken up more efficiently than EVs from benign cells. Though not entirely organ-specific, EVs were incorporated in different amounts, depending on the entity (prostate: lung > liver > brain; kidney: brain > lung > liver; bladder: lung > liver > brain). EV uptake in other organs than lung, liver, brain, and spleen was not observed. Our results suggest a role of EVs in the formation of premetastatic niches and an organotropism in EV uptake, which have to be examined in more detail in further studies.

| S-EPMC8508228 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data