Vesiclepedia is a community-annotated compendium of molecular data on extracellular vesicles.

We argue that the field of extracellular vesicle (EV) biology needs more transparent reporting to facilitate interpretation and replication of experiments. To achieve this, we describe EV-TRACK, a crowdsourcing knowledgebase (http://evtrack.org) that centralizes EV biology and methodology with the goal of stimulating authors, reviewers, editors and funders to put experimental guidelines into practice.

Intercellular communication was long thought to be regulated exclusively through direct contact between cells or via release of soluble molecules that transmit the signal by binding to a suitable receptor on the target cell, and/or via uptake into that cell. With the discovery of small secreted vesicular structures that contain complex cargo, both in their lumen and the lipid membrane that surrounds them, a new frontier of signal transduction was discovered. These “extracellular vesicles” (EV) were initially thought to be garbage bags through which the cell ejected its waste. Whilst this is a major function of one type of EV, i.e., apoptotic bodies, many EVs have intricate functions in intercellular communication and compound exchange; although their physiological roles are still ill-defined. Additionally, it is now becoming increasingly clear that EVs mediate disease progression and therefore studying EVs has ignited significant interests among researchers from various fields of life sciences. Consequently, the research effort into the pathogenic roles of EVs is significantly higher even though their protective roles are not well established. The “Focus on extracellular vesicles” series of reviews highlights the current state of the art regarding various topics in EV research, whilst this review serves as an introductory overview of EVs, their biogenesis and molecular composition.

Exosomes are nanovesicles released by a variety of cells and are detected in body fluids including blood. Recent studies have highlighted the critical application of exosomes as personalized targeted drug delivery vehicles and as reservoirs of disease biomarkers. While these research applications have created significant interest and can be translated into practice, the stability of exosomes needs to be assessed and exosome isolation protocols from blood plasma need to be optimized. To optimize methods to isolate exosomes from blood plasma, we performed a comparative evaluation of three exosome isolation techniques (differential centrifugation coupled with ultracentrifugation, epithelial cell adhesion molecule immunoaffinity pull-down, and OptiPrep(TM) density gradient separation) using normal human plasma. Based on MS, Western blotting and microscopy results, we found that the OptiPrep(TM) density gradient method was superior in isolating pure exosomal populations, devoid of highly abundant plasma proteins. In addition, we assessed the stability of exosomes in plasma over 90 days under various storage conditions. Western blotting analysis using the exosomal marker, TSG101, revealed that exosomes are stable for 90 days. Interestingly, in the context of cellular uptake, the isolated exosomes were able to fuse with target cells revealing that they were indeed biologically active.

Exosomes are a class of extracellular vesicles that are secreted by various cell types. Unlike other extracellular vesicles (ectosomes and apoptotic blebs), exosomes are of endocytic origin. The roles of exosomes in vaccine/drug delivery, intercellular communication and as a possible source of disease biomarkers have sparked immense interest in them, resulting in a plethora of studies. Whilst multidimensional datasets are continuously generated, it is difficult to harness the true potential of the data until they are compiled and made accessible to the biomedical researchers. Here, we describe ExoCarta (http://www.exocarta.org), a manually curated database of exosomal proteins, RNA and lipids. Datasets currently present in ExoCarta are integrated from both published and unpublished exosomal studies. Since its launch in 2009, ExoCarta has been accessed by more than 16,000 unique users. In this article, we discuss the utility of ExoCarta for exosomal research and urge biomedical researchers in the field to deposit their datasets directly to ExoCarta.

Extracellular vesicles are signaling organelles that are released by many cell types and is highly conserved in both prokaryotes and eukaryotes. Based on the mechanism of biogenesis, these membranous vesicles can be classified as exosomes, shedding microvesicles and apoptotic blebs. It is becoming clearer that these extracellular vesicles mediate signal transduction in both autocrine and paracrine fashion by the transfer of proteins and RNA. Whilst the role of extracellular vesicles including exosomes in pathogenesis is well established, very little is known about their function in normal physiological conditions. Recent evidences allude that extracellular vesicles can mediate both protective and pathogenic effects depending on the precise state. In this review, we discuss the involvement of extracellular vesicle as mediators of signal transduction in neurodegenerative diseases and cancer. In addition, the role of extracellular vesicles in mediating Wnt and PI3K signaling pathways is also discussed. Additional findings on the involvement of extracellular vesicles in homeostasis and disease progression will promote a better biological understanding, advance future therapeutic and diagnostic applications.

Extracellular vesicles (EVs) are membranous vesicles that are released by cells. In this study, the role of the Endosomal Sorting Complex Required for Transport (ESCRT) machinery in the biogenesis of yeast EVs was examined. Knockout of components of the ESCRT machinery altered the morphology and size of EVs as well as decreased the abundance of EVs. In contrast, strains with deletions in cell wall biosynthesis genes, produced more EVs than wildtype. Proteomic analysis highlighted the depletion of ESCRT components and enrichment of cell wall remodelling enzymes, glucan synthase subunit Fks1 and chitin synthase Chs3, in yeast EVs. Interestingly, EVs containing Fks1 and Chs3 rescued the yeast cells from antifungal molecules. However, EVs from fks1 ∆ or chs3 ∆ or the vps23 ∆ chs3 ∆ double knockout strain were unable to rescue the yeast cells as compared to vps23 ∆ EVs. Overall, we have identified a potential role for yeast EVs in cell wall remodelling.

Mutations in β-catenin, especially at the residues critical for its degradation, render it constitutively active. Here, we show that mutant β-catenin can be transported via extracellular vesicles (EVs) and activate Wnt signalling pathway in the recipient cells. An integrative proteogenomic analysis identified the presence of mutated β-catenin in EVs secreted by colorectal cancer (CRC) cells. Follow-up experiments established that EVs released from LIM1215 CRC cells stimulated Wnt signalling pathway in the recipient cells with wild-type β-catenin. SILAC-based quantitative proteomics analysis confirmed the transfer of mutant β-catenin to the nucleus of the recipient cells. In vivo tracking of DiR-labelled EVs in mouse implanted with RKO CRC cells revealed its biodistribution, confirmed the activation of Wnt signalling pathway in tumour cells and increased the tumour burden. Overall, for the first time, this study reveals that EVs can transfer mutant βcatenin to the recipient cells and promote cancer progression.