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      Extracellular vesicles: Exosomes, microvesicles, and friends

      review-article
      Author(s): 1 , 2 , , 3
      Publication date (Print):
      Journal: The Journal of Cell Biology
      Publisher: The Rockefeller University Press

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          Abstract

          Cells release into the extracellular environment diverse types of membrane vesicles of endosomal and plasma membrane origin called exosomes and microvesicles, respectively. These extracellular vesicles (EVs) represent an important mode of intercellular communication by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids, and RNA. Deficiencies in our knowledge of the molecular mechanisms for EV formation and lack of methods to interfere with the packaging of cargo or with vesicle release, however, still hamper identification of their physiological relevance in vivo. In this review, we focus on the characterization of EVs and on currently proposed mechanisms for their formation, targeting, and function.

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          Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication.

          J Ratajczak, M Wysoczynski, F Hayek … (2006)
          Normal and malignant cells shed from their surface membranes as well as secrete from the endosomal membrane compartment circular membrane fragments called microvesicles (MV). MV that are released from viable cells are usually smaller in size compared to the apoptotic bodies derived from damaged cells and unlike them do not contain fragmented DNA. Growing experimental evidence indicates that MV are an underappreciated component of the cell environment and play an important pleiotropic role in many biological processes. Generally, MV are enriched in various bioactive molecules and may (i) directly stimulate cells as a kind of 'signaling complex', (ii) transfer membrane receptors, proteins, mRNA and organelles (e.g., mitochondria) between cells and finally (iii) deliver infectious agents into cells (e.g., human immuno deficiency virus, prions). In this review, we discuss the pleiotropic effects of MV that are important for communication between cells, as well as the role of MV in carcinogenesis, coagulation, immune responses and modulation of susceptibility/infectability of cells to retroviruses or prions.
          Article 0 comments Cited 508 times – based on 0 reviews     Review now
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            Exosomal microRNA: a diagnostic marker for lung cancer.

            Guilherme Rabinowits, Cicek Gercel-Taylor, Jamie Day … (2009)
            To date, there is no screening test for lung cancer shown to affect overall mortality. MicroRNAs (miRNAs) are a class of small noncoding RNA genes found to be abnormally expressed in several types of cancer, suggesting a role in the pathogenesis of human cancer. We evaluated the circulating levels of tumor exosomes, exosomal small RNA, and specific exosomal miRNAs in patients with and without lung adenocarcinoma, correlating the levels with the American Joint Committee on Cancer (AJCC) disease stage to validate it as an acceptable marker for diagnosis and prognosis in patients with adenocarcinoma of the lung. To date, 27 patients with lung adenocarcinoma AJCC stages I-IV and 9 controls, all aged 21-80 years, were enrolled in the study. Small RNA was detected in the circulating exosomes. The mean exosome concentration was 2.85 mg/mL (95% CI, 1.94-3.76) for the lung adenocarcinoma group versus 0.77 mg/mL (95% CI, 0.68-0.86) for the control group (P < .001). The mean miRNA concentration was 158.6 ng/mL (95% CI, 145.7-171.5) for the lung adenocarcinoma group versus 68.1 ng/mL (95% CI, 57.2-78.9) for the control group (P < .001). Comparisons between peripheral circulation miRNA-derived exosomes and miRNA-derived tumors indicated that the miRNA signatures were not significantly different. The significant difference in total exosome and miRNA levels between lung cancer patients and controls, and the similarity between the circulating exosomal miRNA and the tumor-derived miRNA patterns, suggest that circulating exosomal miRNA might be useful as a screening test for lung adenocarcinoma. No correlation between the exosomal miRNA levels and the stage of disease can be made at this point.
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              The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins.

              Camilla Raiborg, Harald Stenmark (2009)
              Selective trafficking of membrane proteins to lysosomes for destruction is required for proper cell signalling and metabolism. Ubiquitylation aids this process by specifying which proteins should be transported to the lysosome lumen by the multivesicular endosome pathway. The endosomal sorting complex required for transport (ESCRT) machinery sorts cargo labelled with ubiquitin into invaginations of endosome membranes. Then, through a highly conserved mechanism also used in cytokinesis and viral budding, it mediates the breaking off of the cargo-containing intraluminal vesicles from the perimeter membrane. The involvement of the ESCRT machinery in suppressing diseases such as cancer, neurodegeneration and infections underscores its importance to the cell.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Cell Biol
                Journal ID (iso-abbrev): J. Cell Biol
                Journal ID (hwp): jcb
                Title: The Journal of Cell Biology
                Publisher: The Rockefeller University Press
                ISSN (Print): 0021-9525
                ISSN (Electronic): 1540-8140
                Publication date (Print): 18 February 2013
                Volume: 200
                Issue: 4
                Pages: 373-383
                Affiliations
                [1 ]Institut Curie, Centre de Recherche, F-75248 Paris, Cedex 05, France
                [2 ]Structure and Membrane Compartments, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 144, Paris F-75248, Cedex 05, France
                [3 ]Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, Netherlands
                Author notes
                Correspondence to Graça Raposo: graposo@ 123456curie.fr
                Article
                Publisher ID: 201211138
                DOI: 10.1083/jcb.201211138
                PMC ID: 3575529
                PubMed ID: 23420871
                SO-VID: ff5f90a9-fd8a-4299-8a33-672beb86e2f3
                Copyright © © 2013 Raposo and Stoorvogel
                License:

                This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

                History
                Date received : 27 November 2012
                Date accepted : 22 January 2013
                Categories
                Subject: Reviews
                Subject: Review

                ScienceOpen disciplines: Cell biology
                Data availability:
                ScienceOpen disciplines: Cell biology

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