Role of LBPA and Alix in Multivesicular Liposome Formation and Endosome Organization

Matsuo, Hirotami; Chevallier, Julien; Mayran, Nathalie; Blanc, Isabelle; Ferguson, Charles; Fauré, Julien; Blanc, Nathalie Sartori; Matile, Stefan; Dubochet, Jacques; Sadoul, Rémy; Parton, Robert G.; Vilbois, Francis; Grüenberg, Jean

doi:10.1126/science.1092425

Cited by 619 publications

(590 citation statements)

References 26 publications

Supporting

Mentioning

556

Contrasting

Unclassified

Order By: Relevance

“…Actually ILV release is sectorized in the cell, i.e is limited in some region of the cell periphery, indicating that the whole MVB cell content is not released at once. ___________________________________________________________________________ (a) 14 intralumenal vesicles (ILVs) of about 70 nm of diameter were observed inside an electron microscopy 3 1. Sorting proteins in exosomes :…”

Section: A Biogenesis and Release Of Exosomes By Producer Cells: Fromentioning

confidence: 99%

“…It has been demonstrated that Alix associates with a specific lipid of the late endosomes called Lyso-bisphosphatidic acid [(LBPA), or BMP for bis(monacylglycero)phosphate], in reconstituted liposomes with an interior low pH [14] . LBPA has been shown to be located mainly in late endosomes and ILV [15].…”

Section: Sorting Via the Endosomal Sorting Complex Required For Transmentioning

confidence: 99%

“…Knocking down Alix expression triggers the diminution of the number of MVB in cells. However LBPA by itself when added to a lipid mixture mimicking the composition of the MVB membrane can induce internal budding of small vesicles from large liposomes [14]. Exosomes appeared not to be enriched in LBPA as compared with parental cells [8,25].…”

Section: Sorting Lipids In Exosomes (Figure 2)mentioning

confidence: 99%

See 2 more Smart Citations

Exosomes as intercellular signalosomes and pharmacological effectors

Record

Subra

Silvente-Poirot

et al. 2011

Biochemical Pharmacology

461

331

View full text Add to dashboard Cite

International audienceCell secretion is a general process involved in various biological responses. Exosomes are part of this process and have gained considerable scientific interest in the past five years. Several steps through investigations across the last 20years can explain this interest. First characterized during reticulocyte maturation, they were next characterized as a key player in the immune response and cancer immunotherapy. More recently they were characterized as vectors of mRNAs, miRNAs and also lipid mediators able to act on target cells. They are the only type of vesicles released from an intracellular compartment from cells in viable conditions. They appear as a vectorized signaling system operating from inside a donor cell towards either the periphery, the cytosol, or possibly to the nucleus of target cells. Exosomes from normal cells trigger positive effects, whereas those from pathological ones, such as tumor cells or infected ones may trigger non-positive health effects. Therefore regulating the biogenesis and secretion of exosomes appear as a pharmacological challenge to intervene in various pathophysiologies. Exosome biogenesis and molecular content, interaction with target cells, utilisation as biomarkers, and functional effects in various pathophysiologies are considered in this review

show abstract

Section: A Biogenesis and Release Of Exosomes By Producer Cells: Fromentioning

confidence: 99%

Section: Sorting Via the Endosomal Sorting Complex Required For Transmentioning

confidence: 99%

Section: Sorting Lipids In Exosomes (Figure 2)mentioning

confidence: 99%

See 1 more Smart Citation

Exosomes as intercellular signalosomes and pharmacological effectors

Record

Subra

Silvente-Poirot

et al. 2011

Biochemical Pharmacology

461

331

View full text Add to dashboard Cite

show abstract

“…2,3 Two main pathways are involved in MVB maturation. 4,5 In addition to the ESCRT (endosomal complex required for traffic) proteins, 6 there is increasing evidence that lipids such as lyso-bisphosphatidic acid (LBPA), 7 ceramides 8 and diacylglycerol (DAG) 9 contribute to this membrane invagination process.…”

mentioning

confidence: 99%

Protein kinase D1/2 is involved in the maturation of multivesicular bodies and secretion of exosomes in T and B lymphocytes

et al. 2015

View full text Add to dashboard Cite

Multivesicular bodies (MVBs) are endocytic compartments that enclose intraluminal vesicles (ILVs) formed by inward budding from the limiting membrane of endosomes. In T lymphocytes, these ILV contain Fas ligand (FasL) and are secreted as 'lethal exosomes' following activation-induced fusion of the MVB with the plasma membrane. Diacylglycerol (DAG) and diacylglycerol kinase α (DGKα) regulate MVB maturation and polarized traffic, as well as subsequent secretion of pro-apoptotic exosomes, but the molecular basis underlying these phenomena remains unclear. Here we identify protein kinase D (PKD) family members as DAG effectors involved in MVB genesis and secretion. We show that the inducible secretion of exosomes is enhanced when a constitutively active PKD1 mutant is expressed in T lymphocytes, whereas exosome secretion is impaired in PKD2-deficient mouse T lymphoblasts and in PKD1/3-null B cells. Analysis of PKD2-deficient T lymphoblasts showed the presence of large, immature MVB-like vesicles and demonstrated defects in cytotoxic activity and in activation-induced cell death. Using pharmacological and genetic tools, we show that DGKα regulates PKD1/2 subcellular localization and activation. Our studies demonstrate that PKD1/2 is a key regulator of MVB maturation and exosome secretion, and constitutes a mediator of the DGKα effect on MVB secretory traffic. Exosomes are nanovesicles that form as intraluminal vesicles (ILVs) inside multivesicular bodies (MVBs) and are then secreted by numerous cell types. 1 ILVs are generated by inward budding of late endosome limiting membrane in a precisely regulated maturation process. 2,3 Two main pathways are involved in MVB maturation. 4,5 In addition to the ESCRT (endosomal complex required for traffic) proteins, 6 there is increasing evidence that lipids such as lyso-bisphosphatidic acid (LBPA), 7 ceramides 8 and diacylglycerol (DAG) 9 contribute to this membrane invagination process.Exosomes participate in many biological processes related to T-cell receptor (TCR)-triggered immune responses, including T lymphocyte-mediated cytotoxicity and activationinduced cell death (AICD), antigen presentation and intercellular miRNA exchange. [10][11][12][13][14][15] The discovery of exosome involvement in these responses increased interest in the regulation of exosome biogenesis and secretory traffic, with special attention to the contribution of lipids such as ceramide and DAG, as well as DAG-binding proteins. 14,16-21 These studies suggest that positive and negative DAG regulators may control secretory traffic. By transforming DAG into phosphatidic acid (PA), diacylglycerol kinase α (DGKα) is essential for the negative control of DAG function in T lymphocytes. 22 DGKα translocates transiently to the T-cell membrane after human muscarinic type 1 receptor (HM1R) triggering or to the immune synapse (IS) after TCR stimulation; at these subcellular locations, DGKα acts as a negative modulator of phospholipase C (PLC)-generated DAG. 23,24 The secretory vesicle pathway involves several DAGc...

show abstract

“…Lorsque des anticorps se liant au LBPA sont internalisés, le trafic du cholestérol, des M6PR ainsi que l'infection par VSV sont diminués, suggérant que l'interférence avec ce lipide perturbe la dynamique des membranes internes [3,5,6]. De plus, des expériences faites sur des liposomes ont montré que le LBPA peut induire l'invagination de membranes, phénomène régulé par la protéine Alix [7]. Le LBPA et Alix pourraient donc être responsable de l'invagination de la membrane limitante.…”

Section: L'endocytose Cheval De Troie Pour L'infection Viraleunclassified

L’endocytose, cheval de Troie pour l’infection virale

Luyet

Grüenberg

2005

Med Sci (Paris)

Self Cite

View full text Add to dashboard Cite

NOUVELLES MAGAZINE 909M/S n° 11, vol. 21, novembre 2005 d'une classification des deux sexes en deux espèces différentes (et pour la première fois d'une espèce dont tous les individus seraient des mâles), puisque mâles et femelles ont des trajectoires évolutives séparées et n'ont pas de descendance fertile [9]. Dans ce système, les deux sexes demeurent affiliés non pas par des échan-ges de gènes mais par une surprenante exploitation parasitique des femelles par les mâles et par la production en commun d'ouvrières stériles assurant le fonctionnement de la colonie. ◊

show abstract

Role of LBPA and Alix in Multivesicular Liposome Formation and Endosome Organization

Cited by 619 publications

References 26 publications

Exosomes as intercellular signalosomes and pharmacological effectors

Exosomes as intercellular signalosomes and pharmacological effectors

Protein kinase D1/2 is involved in the maturation of multivesicular bodies and secretion of exosomes in T and B lymphocytes

L’endocytose, cheval de Troie pour l’infection virale

Contact Info

Product

Resources

About