Itinerant exosomes: emerging roles in cell and tissue polarity. Trends Cell Biol

Margaret M. Dyson Vision Research Institute, Department of Ophthalmology, Weill Medical College of Cornell University, New York, NY 10021, USA.
Trends in cell biology (Impact Factor: 12.01). 06/2008; 18(5):199-209. DOI: 10.1016/j.tcb.2008.03.002
Source: PubMed

ABSTRACT Cells use secreted signals (e.g. chemokines and growth factors) and sophisticated vehicles such as argosomes, cytonemes, tunneling nanotubes and exosomes to relay important information to other cells, often over large distances. Exosomes, 30-100-nm intraluminal vesicles of multivesicular bodies (MVB) released upon exocytic fusion of the MVB with the plasma membrane, are increasingly recognized as a novel mode of cell-independent communication. Exosomes have been shown to function in antigen presentation and tumor metastasis, and in transmitting infectious agents. However, little is known about the biogenesis and function of exosomes in polarized cells. In this review, we discuss new evidence suggesting that exosomes participate in the transport of morphogens and RNA, and thus influence cell polarity and developmental patterning of tissues.

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Available from: Aparna Lakkaraju, Jul 09, 2014
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    • "A member of the RAB GTPase family, RAB5, is a key regulator of endocytic trafficking and acts as a molecular switch by cycling active GTP-and inactive GDP-bound states. In the animal system, RAB5 is well characterized and regulates various endosomal functions (Somsel Rodman and Wandinger-Ness 2000, Benmerah 2004, Russell et al. 2006, Lakkaraju and Rodriguez-Boulan 2008, Villarroel-Campos et al. 2014). Plants also harbor orthologs of animal RAB5; in addition, land plants harbor the plant-unique RAB5 group, the ARA6 group (Ueda et al. 2001, Ebine et al. 2011). "
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    ABSTRACT: Endosomal trafficking plays integral roles in various eukaryotic cell activities. In animal cells, a member of the RAB GTPase family, RAB5, is a key regulator of various endosomal functions. In addition to orthologs of animal RAB5, plants harbor the plant-specific RAB5 group, the ARA6 group, which is conserved in land plant lineages. In Arabidopsis thaliana, ARA6 and conventional RAB5 act in distinct endosomal trafficking pathways; ARA6 mediates trafficking from endosomes to the plasma membrane, whereas conventional RAB5 acts in endocytic and vacuolar trafficking pathways. ARA6 is also required for normal salt and osmotic stress tolerance, although the functional link between ARA6 and stress tolerance remains unclear. In this study, we investigated ARA6 function in stress tolerance by monitoring broad-scale changes in gene expression in the ara6 mutant. A comparison of the expression profiles between wild-type and ara6-1 plants revealed that the expression of the Qua-Quine Starch (QQS) gene was significantly affected by the ara6-1 mutation. QQS is involved in starch homeostasis, consistent with the starch content decreasing in the ara6 mutants to approximately 60% of that of the wild-type plant. In contrast, the free and total glucose content increased in the ara6 mutants. Moreover, the proliferation of Pseudomonas syringae pv. tomato DC3000 was repressed in ara6 mutants, which could be attributed to the elevated sugar content. These results suggest that ARA6 is responsible for starch and sugar homeostasis, most likely through the function of QQS. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For Permissions, please e-mail:
    Plant and Cell Physiology 02/2015; 56(6). DOI:10.1093/pcp/pcv029 · 4.93 Impact Factor
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    • "Different kinds of EVs can be isolated from all body fluids: blood plasma, serum, urine, saliva, breast milk, bronchial lavage fluid, amniotic fluid, cerebrospinal fluid, and malignant ascites (2) and have been envisioned as a novel mechanism of horizontal gene transfer. EVs contain a specific composition of lipids, mRNA, regulatory microRNAs, as well as proteins in a functionally active form (3). The transfer of this material can regulate gene expression and alter the fate of target cells (4), which may become activated, differentiated, or dedifferentiated according to the information received. As a result, EVs represent an important tool for intercellular communication and therefore play a key role in the regulation of physiological as well as pathological processes. "
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    ABSTRACT: Extracellular vesicles (EVs) represent a novel mechanism of intercellular communication as vehicles for intercellular transfer of functional membrane and cytosolic proteins, lipids, and RNAs. Microvesicles, ectosomes, shedding vesicles, microparticles, and exosomes are the most common terms to refer to the different kinds of EVs based on their origin, composition, size, and density. Exosomes have an endosomal origin and are released by many different cell types, participating in different physiological and/or pathological processes. Depending on their origin, they can alter the fate of recipient cells according to the information transferred. In the last two decades, EVs have become the focus of many studies because of their putative use as non-invasive biomarkers and their potential in bioengineering and clinical applications. In order to exploit this ability of EVs many aspects of their biology should be deciphered. Here, we review the mechanisms involved in EV biogenesis, assembly, recruitment of selected proteins, and genetic material as well as the uptake mechanisms by target cells in an effort to understand EV functions and their utility in clinical applications. In these contexts, the role of proteins from the tetraspanin superfamily, which are among the most abundant membrane proteins of EVs, will be highlighted.
    Frontiers in Immunology 09/2014; 5:442. DOI:10.3389/fimmu.2014.00442
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    • "Exosomes can interact with recipient target cells via different mechanisms such as fusion with the plasma membrane or adhesion to corresponding receptors on the plasma membrane [61]. Several lines of evidence suggest that induction of intracellular calcium [61], overexpression of Rab11 or citron kinase [62] as well as a reduction in membrane cholesterol, or inhibition of cholesterol biosynthesis [63], could stimulate the release of exosomes into the microenvironment. "
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    ABSTRACT: Intercellular interactions are essential for basic cellular activities and errors in either receiving or transferring these signals have shown to cause pathological conditions. These signals are not only regulated by membrane surface molecules but also by soluble secreted proteins, thereby allowing for an exquisite coordination of cell functions. Exosomes are released by cells upon fusion of multivesicular bodies (MVB) with the plasma membrane. Their envelope reflects their cellular origin and their surface and internal contents include important signaling components. Exosomes contain a wide variety of proteins, lipids, RNAs, non-transcribed RNAs, miRNAs and small RNAs that are representative to their cellular origin and shuttle from donor cells to recipient cells. The exosome formation cargo content and delivery is of immense biological interest because exosomes are believed to play major roles in various pathological conditions, and therefore provide unique opportunities for biomarker discovery and development of non-invasive diagnostics when examined in biological fluids such as urine and blood plasma. For example, circulating miRNAs in exosomes have been applied as functional biomarkers for diagnosis and outcomes prediction, while synthetic miRNAs in polymer-based nanoparticles are applicable for therapeutics. This review provides insights into the composition and functional properties of exosomes, and focuses on their potential value as diagnostic markers in the context of cardiovascular disease risk estimates in children who suffer from conditions associated with heightened prevalence of adverse cardiovascular disease, namely obesity and sleep-disordered-breathing.
    Journal of Translational Medicine 06/2014; 12(1):162. DOI:10.1186/1479-5876-12-162 · 3.93 Impact Factor
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