Cutting Edge: Regulation of Exosome Secretion by the Integral MAL Protein in T Cells

Ventimiglia, Leandro N.; Fernández-Martín, Laura; Martínez‐Alonso, Emma; Antón, Olga M.; Guerra, Milagros; Martı́nez-Menárguez, José A.; Andrés, Germán; Alonso, Miguel A.

doi:10.4049/jimmunol.1500891

Cited by 38 publications

(41 citation statements)

References 17 publications

(15 reference statements)

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“…The conditioned media were collected (3) and centrifuged at 500g (4) to eliminate the cells (5), and the supernatant was collected (6) and centrifuged at 2000g (7) to eliminate the cell debris (8). To isolate MVs, the supernatant was collected (9a) and centrifuged at 20 000g (10a).…”

Section: Transmission Electron Microscopymentioning

confidence: 99%

Analysis of the thrombotic and fibrinolytic activities of tumor cell–derived extracellular vesicles

Durrieu¹,

Bharadwaj²,

Waisman

2018

Blood Advances

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Key Points• Microvesicles, but not exosomes, from tumor cells have thrombotic activity.• Tumor derivedexosomes can confer increased plasmingenerating capacity to a recipient cell.Exosomes and microvesicles (MVs) are small extracellular vesicles secreted by tumor cells and are suggested to contribute to the thrombotic events that commonly occur in patients with advanced malignancies. Paradoxically, these vesicles have been reported to also possess fibrinolytic activity. To determine whether thrombotic or fibrinolytic activity is a predominant characteristic of these extracellular vesicles, we prepared exosomes andMVs from 2 breast cancer cell lines (MDA-MB-231 and MCF7), a lung cancer cell line (A549), and a leukemia cell line (NB4) and assayed their thrombotic and fibrinolytic activities.We observed that thrombotic activity was a common feature of MVs but not exosomes.

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Section: Transmission Electron Microscopymentioning

confidence: 99%

Analysis of the thrombotic and fibrinolytic activities of tumor cell–derived extracellular vesicles

Durrieu¹,

Bharadwaj²,

Waisman

2018

Blood Advances

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“…Exosomes have high contents of cholesterol, sphingomyelin, ceramide and ganglioside GM3 (Wubbolts et al, 2003 ; Subra et al, 2007 ; Trajkovic et al, 2008 ; Llorente et al, 2013 ; Bosque et al, 2016 ), which are all of them lipids that are concentrated in condensed membrane domains often referred to as membrane rafts (Lingwood and Simons, 2010 ). Consistent with this observation, exosomes are enriched in proteins associated with these specialized membranes (Wubbolts et al, 2003 ; Staubach et al, 2009 ; Dubois et al, 2015 ), including molecules whose protein moiety is linked to the external leaflet of the membrane by a glycosylphosphatidylinositol anchor, such as CD59 and the enzyme acetylcholinesterase (Johnstone et al, 1987 ; Rooney et al, 1993 ; Rabesandratana et al, 1998 ; De Gassart et al, 2003 ) or is linked to the internal leaflet by fatty acids, such as Src-family tyrosine kinases (De Gassart et al, 2003 ), or by proteins with membrane-associated domains, such as caveolin-1 and the membrane tetraspanning MAL protein (Llorente et al, 2004 ; Ventimiglia et al, 2015 ).…”

Section: General Mechanisms Of Exosome Biogenesismentioning

confidence: 99%

Biogenesis and Function of T Cell-Derived Exosomes

Ventimiglia

Alonso

2016

Front. Cell Dev. Biol.

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Exosomes are a particular type of extracellular vesicle, characterized by their endosomal origin as intraluminal vesicles present in large endosomes with a multivesicular structure. After these endosomes fuse with the plasma membrane, exosomes are secreted into the extracellular space. The ability of exosomes to carry and selectively deliver bioactive molecules (e.g., lipids, proteins, and nucleic acids) confers on them the capacity to modulate the activity of receptor cells, even if these cells are located in distant tissues or organs. Since exosomal cargo depends on cell type, a detailed understanding of the mechanisms that regulate the biochemical composition of exosomes is fundamental to a comprehensive view of exosome function. Here, we review the latest advances concerning exosome function and biogenesis in T cells, with particular focus on the mechanism of protein sorting at multivesicular endosomes. Exosomes secreted by specific T-cell subsets can modulate the activity of immune cells, including other T-cell subsets. Ceramide, tetraspanins and MAL have been revealed to be important in exosome biogenesis by T cells. These molecules, therefore, constitute potential molecular targets for artificially modulating exosome production and, hence, the immune response for therapeutic purposes.

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“…The presence of MAL protein in myelin structures and myelinating oligodendrocytes would explain the specific binding of Etx to myelin (9) and the demyelinating effect of the toxin (10,11). The presence of MAL protein in lymphocytes has been mainly linked to the maturation of T cells (24), intracellular membrane traffic (27), or exosome secretion (28). However, the possible effect of Etx on MAL protein-expressing lymphocyte-derived cells is not known.…”

mentioning

confidence: 99%

The Cytotoxicity of Epsilon Toxin from Clostridium perfringens on Lymphocytes Is Mediated by MAL Protein Expression

Blanch

Dorca-Arévalo

Not

et al. 2018

Molecular and Cellular Biology

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Epsilon toxin (Etx) from is a pore-forming protein that crosses the blood-brain barrier, binds to myelin, and, hence, has been suggested to be a putative agent for the onset of multiple sclerosis, a demyelinating neuroinflammatory disease. Recently, myelin and lymphocyte (MAL) protein has been identified to be a key protein in the cytotoxic effect of Etx; however, the association of Etx with the immune system remains a central question. Here, we show that Etx selectively recognizes and kills only human cell lines expressing MAL protein through a direct Etx-MAL protein interaction. Experiments on lymphocytic cell lines revealed that MAL protein-expressing T cells, but not B cells, are sensitive to Etx and reveal that the toxin may be used as a molecular tool to distinguish subpopulations of lymphocytes. The overall results open the door to investigation of the role of Etx and on inflammatory and autoimmune diseases like multiple sclerosis.

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Cutting Edge: Regulation of Exosome Secretion by the Integral MAL Protein in T Cells

Cited by 38 publications

References 17 publications

Analysis of the thrombotic and fibrinolytic activities of tumor cell–derived extracellular vesicles

Analysis of the thrombotic and fibrinolytic activities of tumor cell–derived extracellular vesicles

Biogenesis and Function of T Cell-Derived Exosomes

The Cytotoxicity of Epsilon Toxin from Clostridium perfringens on Lymphocytes Is Mediated by MAL Protein Expression

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