Fas Death Receptor Enhances Endocytic Membrane Traffic Converging into the Golgi Region

Esposti, Mauro Degli; Tour, Julien; Ouasti, Sihem; Ivanova, Saška; Matarrese, Paola; Malorni, Walter; Khosravi‐Far, Roya

doi:10.1091/mbc.e08-09-0925

Cited by 22 publications

(37 citation statements)

References 52 publications

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“…Our results suggested the reduction of Tumor Necrosis Factorrelated apoptosis-inducing ligand receptors 2 might be the reason Some investigators have reported that death receptors, such as Fas/CD95, undergo rapid internalization after triggering [Algeciras-Schimnich et al, 2002] and that Fas signaling enhances exocytosis after the initial wave of increased endocytosis [Reinehr and Haussinger, 2008]. Esposti also reported that the Fas enhances endocytic membrane traffic converging into the Golgi region [Degli Esposti et al, 2009]. Many recent studies have examined the role of Fas-mediated cell death in the vasculature, and Fas/FasL-mediated apoptosis has been proposed to play a role in physiological and pathological cell turnover in the vasculature [Fukuo et al, 1997;Sata and Walsh, 1998;Suhara et al, 1998].…”

Section: Discussionsupporting

confidence: 51%

FasL/Fas pathway is involved in dengue virus induced apoptosis of the vascular endothelial cells

Liao¹,

Xu²,

Huang

2010

Journal of Medical Virology

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The hallmark of the dengue hemorrhagic fever/dengue shock syndrome is hematologic abnormality. The pathogenesis of dengue hemorrhagic fever/dengue shock syndrome remains unknown. Our work showed that the dengue virus serotype-2 induced apoptosis in human umbilical vein endothelial cells. Fas (CD95), Tumor Necrosis Factor receptors, and Tumor Necrosis Factor-related apoptosis-inducing ligand receptors are the most common death receptors, which can induce apoptosis. Compared with the untreated human umbilical vein endothelial cells, Fas expression was increased both in the mRNA level and on the surface of infected human umbilical vein endothelial cells. FasL was expressed at similar levels on human umbilical vein endothelial cells over a course of dengue virus serotype-2 infection, but the expression in mRNA level was increased in infected human umbilical vein endothelial cells. It is possible that there is soluble FasL secreted from human umbilical vein endothelial cells in the supernatant. Tumor Necrosis Factor-related apoptosis-inducing ligand receptor 1 and Tumor Necrosis Factor receptors 1-2 were constantly very low, whereas Tumor Necrosis Factor-related apoptosis-inducing ligand receptors 2-4 decreased after dengue virus serotype-2 infection. This result suggested that dengue virus serotype-2 may inhibit Tumor Necrosis Factor-related apoptosis-inducing ligand receptors-induced apoptosis. The apoptotic rates in human umbilical vein endothelial cells were decreased upon the addition of caspase family inhibitors. In addition, activated caspase 8 and caspase 3 were also observed by Western blot following dengue virus serotype-2 infection. Thus, it is shown that the Fas/FasL pathway may participate in dengue virus-induced apoptosis of vascular endothelial cells in vitro.

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Section: Discussionsupporting

confidence: 51%

FasL/Fas pathway is involved in dengue virus induced apoptosis of the vascular endothelial cells

Liao¹,

Xu²,

Huang

2010

Journal of Medical Virology

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“…Interestingly, it had been reported that CD95 activation induces profound changes in intracellular membrane trafficking, dependent on caspase 8 activation, including also the secretory pathway (37). Our identification of a secretory/exocytic pathway of A-SMase activation offers a link between these events.…”

Section: Discussionsupporting

confidence: 50%

Syntaxin 4 Is Required for Acid Sphingomyelinase Activity and Apoptotic Function

Perrotta

Bizzozero

Cazzato

et al. 2010

Journal of Biological Chemistry

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Acid sphingomyelinase (A-SMase) is an important enzyme in sphingolipid metabolism and plays key roles in apoptosis, immunity, development, and cancer. In addition, it mediates cytotoxicity of cisplatin and some other chemotherapeutic drugs. The mechanism of A-SMase activation is still undefined. We now demonstrate that, upon CD95 stimulation, ASMase is activated through translocation from intracellular compartments to the plasma membrane in an exocytic pathway requiring the t-SNARE protein syntaxin 4. Indeed, downregulation of syntaxin 4 inhibits A-SMase translocation and activation induced by CD95 stimulation. This leads to inhibition of the CD95-triggered signaling events, including caspase 3 and 9 activation and apoptosis, activation of the survival pathway involving the protein kinase Akt, and important changes in cell cycle and proliferation. The molecular interaction between A-SMase and syntaxin 4 was not known and clarifies the mechanism of A-SMase activation. The novel actions of syntaxin 4 in sphingolipid metabolism and exocytosis we describe here define signaling mechanisms of broad relevance in cell pathophysiology.Acid sphingomyelinase (A-SMase) 3 (EC 3.1.4.12) is a phosphodiesterase that catalyzes the hydrolysis of membrane lipid sphingomyelin to ceramide and phosphorylcholine. The enzyme plays important roles in pathophysiology, as it mediates the action of several apoptogenic molecules, cytokines, and neurotrophins, regulating neuronal function, immunity, and infections (1-3).Enzymatic dysfunction of A-SMase leads to Niemann-Pick diseases types A and B (4). The enzyme is also important in cancer development and therapy; tumor growth is enhanced in A-SMase knock-out mice (5), and the enzyme contributes significantly to the cytotoxic effects of several anticancer drugs (6 -9). The biology of A-SMase under resting conditions, including its localization to lysosomal compartments, has been clarified (6, 9). Less clear is how A-SMase is activated. Activation has been suggested to require translocation from intracellular compartments to the extracellular surface of the cell through pathways as yet unknown (3, 9) or to occur within the lysosomes (10). Elucidating the molecular mechanisms of A-SMase activation is of biological relevance and might reveal novel candidate targets for therapy, including cancer therapy.Using U373, a human glioma cell line expressing the death receptor CD95, we have now established that translocation of A-SMase to the plasma membrane is required for its early activation, that this process takes place by exocytosis, and that a key role in it is played by syntaxin 4, an ubiquitously expressed t-SNARE implicated in several regulated exocytic pathways including the translocation of Glut4 to the plasma membrane, exocytosis of secretory granules, and the calcium-dependent release of lysosomes (11,12). Furthermore, we demonstrate that the blockade of syntaxin 4-dependent exocytosis inhibits CD95 receptor clustering and internalization, caspase activation and loss of mitochondrial membr...

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“…Given the rapid loss of free thiol content of Fas that is already apparent after 5 min, these events are induced rapidly and are unlikely to require internalization of Fas (12) or assembly of the DISC (Fig. 4C).…”

Section: Discussionmentioning

confidence: 99%

Oxidative Processing of Latent Fas in the Endoplasmic Reticulum Controls the Strength of Apoptosis

Anathy

Roberson

Cunniff

et al. 2012

Molecular and Cellular Biology

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Fas Death Receptor Enhances Endocytic Membrane Traffic Converging into the Golgi Region

Cited by 22 publications

References 52 publications

FasL/Fas pathway is involved in dengue virus induced apoptosis of the vascular endothelial cells

FasL/Fas pathway is involved in dengue virus induced apoptosis of the vascular endothelial cells

Syntaxin 4 Is Required for Acid Sphingomyelinase Activity and Apoptotic Function

Oxidative Processing of Latent Fas in the Endoplasmic Reticulum Controls the Strength of Apoptosis

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