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      Q&A: What are exosomes, exactly?

      BMC Biology

      BioMed Central

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          Abstract

          Exosomes are extracellular vesicles first described as such 30 years ago and since implicated in cell–cell communication and the transmission of disease states, and explored as a means of drug discovery. Yet fundamental questions about their biology remain unanswered. Here I explore what exosomes are, highlight the difficulties in studying them and explain the current definition and some of the outstanding issues in exosome biology.

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          Most cited references 17

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          Proteomic analysis of dendritic cell-derived exosomes: a secreted subcellular compartment distinct from apoptotic vesicles.

          Dendritic cells constitutively secrete a population of small (50-90 nm diameter) Ag-presenting vesicles called exosomes. When sensitized with tumor antigenic peptides, dendritic cells produce exosomes, which stimulate anti-tumor immune responses and the rejection of established tumors in mice. Using a systematic proteomic approach, we establish the first extensive protein map of a particular exosome population; 21 new exosomal proteins were thus identified. Most proteins present in exosomes are related to endocytic compartments. New exosomal residents include cytosolic proteins most likely involved in exosome biogenesis and function, mainly cytoskeleton-related (cofilin, profilin I, and elongation factor 1alpha) and intracellular membrane transport and signaling factors (such as several annexins, rab 7 and 11, rap1B, and syntenin). Importantly, we also identified a novel category of exosomal proteins related to apoptosis: thioredoxin peroxidase II, Alix, 14-3-3, and galectin-3. These findings led us to analyze possible structural relationships between exosomes and microvesicles released by apoptotic cells. We show that although they both represent secreted populations of membrane vesicles relevant to immune responses, exosomes and apoptotic vesicles are biochemically and morphologically distinct. Therefore, in addition to cytokines, dendritic cells produce a specific population of membrane vesicles, exosomes, with unique molecular composition and strong immunostimulating properties.
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            Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes

            Using ferritin-labeled protein A and colloidal gold-labeled anti-rabbit IgG, the fate of the sheep transferrin receptor has been followed microscopically during reticulocyte maturation in vitro. After a few minutes of incubation at 37 degrees C, the receptor is found on the cell surface or in simple vesicles of 100-200 nm, in which the receptor appears to line the limiting membrane of the vesicles. With time (60 min or longer), large multivesicular elements (MVEs) appear whose diameter may reach 1-1.5 micron. Inside these large MVEs are round bodies of approximately 50-nm diam that bear the receptor at their external surfaces. The limiting membrane of the large MVEs is relatively free from receptor. When the large MVEs fuse with the plasma membrane, their contents, the 50-nm bodies, are released into the medium. The 50-nm bodies appear to arise by budding from the limiting membrane of the intracellular vesicles. Removal of surface receptor with pronase does not prevent exocytosis of internalized receptor. It is proposed that the exocytosis of the approximately 50-nm bodies represents the mechanism by which the transferrin receptor is shed during reticulocyte maturation.
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              The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC.

              Since their discovery almost two decades ago, microRNAs (miRNAs) have been shown to function by post-transcriptionally regulating protein accumulation. Understanding how miRNAs silence targeted mRNAs has been the focus of intensive research. Multiple models have been proposed, with few mechanistic details having been worked out. However, the past few years have witnessed a quantum leap forward in our understanding of the molecular mechanics of miRNA-mediated gene silencing. In this review we describe recent discoveries, with an emphasis on how miRISC post-transcriptionally controls gene expression by inhibiting translation and/or initiating mRNA decay, and how trans-acting factors control miRNA action.
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                Author and article information

                Contributors
                je333@cam.ac.uk
                Journal
                BMC Biol
                BMC Biol
                BMC Biology
                BioMed Central (London )
                1741-7007
                13 June 2016
                13 June 2016
                2016
                : 14
                Affiliations
                Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge, CB2 0XY UK
                Article
                268
                10.1186/s12915-016-0268-z
                4906597
                27296830
                © Edgar. 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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                Life sciences

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