Proteolipidic Composition of Exosomes Changes during Reticulocyte Maturation

Carayon, Kévin; Chaoui, Karima; Ronzier, Elsa; Lazar, Ikrame; Bertrand‐Michel, Justine; Roques, Véronique; Balor, Stéphanie; Tercé, François; Lopez, André; Salomé, Laurence; Joly, Etienne

doi:10.1074/jbc.m111.257444

Cited by 161 publications

(135 citation statements)

References 57 publications

Supporting

Mentioning

123

Contrasting

Unclassified

Order By: Relevance

“…34,35 Nevertheless, differences in phospholipid molecular species composition and higher neutral lipid content distinguish LVPs between specific TRLs defined by their density. Interestingly, most LVPs resemble empty, nucleocapsid-free subviral particles, similar to recombinant subviral envelope particles produced in vitro, whereas nucleocapsid-containing LVPs are only a subset of the whole LVP ensemble.…”

Section: Discussionmentioning

confidence: 99%

High plasma level of nucleocapsid-free envelope glycoprotein-positive lipoproteins in hepatitis C patients

et al. 2012

View full text Add to dashboard Cite

Hepatitis C virus (HCV) particles associate viral and lipoprotein moieties to form hybrid lipoviral particles (LVPs). Cell culture-produced HCV (HCVcc) and ex vivo-characterized LVPs primarily differ by their apolipoprotein (apo) B content, which is low for HCVcc, but high for LVPs. Recombinant nucleocapsid-free subviral LVPs are assembled and secreted by apoB-producing cell lines. To determine whether such subviral particles circulate in HCV-infected individuals, LVPs complexed with immunoglobulin were precipitated with protein A from low-density plasma fractions of 36 hepatitis C patients, and their lipid content, apolipoprotein profile, and viral composition were determined. HCV RNA in LVPs was quantified and molar ratios of apoB and HCV genome copy number were calculated. LVPs lipidome from four patients was determined via electrospray ionization/tandem mass spectrometry. Protein A-purified LVPs contained at least the envelope glycoprotein E2 and E2-specific antibodies. LVPs were present in every patient and were characterized by high lipid content, presence of apolipoproteins characteristic of triglyceride-rich lipoproteins (TRLs), HCV RNA, and viral glycoprotein. Importantly, save for four patients, LVPs fractions contained large amounts of apoB, with on average more than 1 3 10 6 apoB molecules per HCV RNA genome. Because there is one apoB molecule per TRL, this ratio suggested that most LVPs are nucleocapsid-free, envelope glycoprotein-containing subviral particles. LVPs and TRLs had similar composition of triacylglycerol and phospholipid classes. Conclusion: LVPs are a mixed population of particles, comprising predominantly subviral particles that represent a distinct class of modified lipoproteins within the TRL family. (HEPATOLOGY 2012;56:39-48) H epatitis C virus (HCV) is a member of the Flaviviridae family and a major cause of chronic hepatitis often leading to liver cirrhosis and hepatocellular carcinoma. 1 Chronic hepatitis C is a complex disease associated with host metabolic modifications resulting in a unique metabolic syndrome including insulin resistance, liver steatosis, and hypobetalipoproteinemia. 2,3 The most striking link between HCV and lipids resides in the association of HCV particles with lipoproteins. 4,5 Indeed, HCV virions with a density <1.06 g/mL are associated with lipoproteins, thus forming hybrid particles known as lipoviral particles (LVPs). These low-density viral particles are globular, rich in triacylglycerol and total cholesterol (TChol) and contain the viral envelope glycoproteins and nucleocapsid (composed of HCV RNA and core protein). In addition, LVPs contain all the apolipoproteins (apo) that define the triacylglycerolrich lipoproteins (TRLs). Indeed, apolipoprotein (apo) B, apoE, apoCI, apoCII, and apoCIII, all of which characterize very low-density, intermediate-density, and low-density lipoproteins (VLDL, IDL, and LDL,

show abstract

Section: Discussionmentioning

confidence: 99%

High plasma level of nucleocapsid-free envelope glycoprotein-positive lipoproteins in hepatitis C patients

et al. 2012

View full text Add to dashboard Cite

show abstract

“…PLP-containing exosomes) in a given cell type, it is in our opinion difficult to extrapolate that all exosome populations are ESCRT independent. As suggested before by an extensive proteomic analysis of exosomes secreted at different stages of reticulocyte maturation (Carayon et al, 2011), different cargos can be sorted by distinct mechanisms, which contributes to such heterogeneity of ILVs. Our results indicate that loss of function of selected ESCRT components, which in some cases decreases (HRS, STAM1, TSG101) or increases (VPS4B) the amount of vesicles and cargo associated with vesicles, also modulates the nature and protein contents of the vesicles.…”

Section: Discussionmentioning

confidence: 99%

Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles

Colombo

Moita

Niel

et al. 2013

Journal of Cell Science

1,119

1,109

View full text Add to dashboard Cite

SummaryExosomes are extracellular vesicles (EVs) secreted upon fusion of endosomal multivesicular bodies (MVBs) with the plasma membrane. The mechanisms involved in their biogenesis have not yet been fully identified although they could be used to modulate exosome formation and therefore are a promising tool in understanding exosome functions. We have performed an RNA interference screen targeting 23 components of the endosomal sorting complex required for transport (ESCRT) machinery and associated proteins in MHC class II (MHC II)-expressing HeLa-CIITA cells. Silencing of HRS, STAM1 or TSG101 reduced the secretion of EV-associated CD63 and MHC II but each gene altered differently the size and/or protein composition of secreted EVs, as quantified by immuno-electron microscopy. By contrast, depletion of VPS4B augmented this secretion while not altering the features of EVs. For several other ESCRT subunits, it was not possible to draw any conclusions about their involvement in exosome biogenesis from the screen. Interestingly, silencing of ALIX increased MHC II exosomal secretion, as a result of an overall increase in intracellular MHC II protein and mRNA levels. In human dendritic cells (DCs), ALIX depletion also increased MHC II in the cells, but not in the released CD63-positive EVs. Such differences could be attributed to a greater heterogeneity in size, and higher MHC II and lower CD63 levels in vesicles recovered from DCs as compared with HeLa-CIITA. The results reveal a role for selected ESCRT components and accessory proteins in exosome secretion and composition by HeLa-CIITA. They also highlight biogenetic differences in vesicles secreted by a tumour cell line and primary DCs.

show abstract

“…Alternatively, the direct quantification of placenta-derived exosomes from total purified exosomes using PLAP as a placenta-specific marker has been achieved. [79][80][81][82][83][84][85] In contrast to immunocapture methods, this method eliminates inaccuracies attributed to the lower exosomal yield obtained using immunocapture techniques. However, the direct quantification of placentaderived exosomes in maternal circulation is largely dependent on the purity of the exosomal fraction.…”

mentioning

confidence: 99%

Placenta-derived exosomes: potential biomarkers of preeclampsia

Pillay¹,

Moodley²,

Moodley³

et al. 2017

IJN

107

View full text Add to dashboard Cite

Preeclampsia remains a leading cause of maternal and fetal mortality, due to ineffective treatment and diagnostic strategies, compounded by the lack of clarity on the etiology of the disorder. Although several clinical and biological markers of preeclampsia have been evaluated, they have proven to be ineffective in providing a definitive diagnosis during the various stages of the disorder. Exosomes have emerged as ideal biomarkers of pathological states, such as cancer, and have more recently gained interest in pregnancy-related complications, due to their role in cellular communication in normal and complicated pregnancies. This occurs as a result of the specific placenta-derived exosomal molecular cargo, which may be involved in normal pregnancy-associated immunological events, such as the maintenance of maternal–fetal tolerance. This review provides perspectives on placenta-derived exosomes as possible biomarkers for the diagnosis/prognosis of preeclampsia. Using keywords, online databases were searched to identify relevant publications to review the potential use of placenta-derived exosomes as biomarkers of preeclampsia.

show abstract

Proteolipidic Composition of Exosomes Changes during Reticulocyte Maturation

Cited by 161 publications

References 57 publications

High plasma level of nucleocapsid-free envelope glycoprotein-positive lipoproteins in hepatitis C patients

High plasma level of nucleocapsid-free envelope glycoprotein-positive lipoproteins in hepatitis C patients

Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles

Placenta-derived exosomes: potential biomarkers of preeclampsia

Contact Info

Product

Resources

About