The role of receptor internalization in CD95 signaling

Lee, Kyeong Hee; Feig, Christine; Tchikov, Vladimir; Schickel, Robert; Hallas, Cora; Schütze, Stefan; Marynen, Peter; Chan, Andrew C.

doi:10.1038/sj.emboj.7601016

Cited by 212 publications

(260 citation statements)

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“…Ezrin-actin association is reported to be required for endocytosis of Fas in mouse embryonic fibroblasts and L12.10 cells (Piazzolla et al, 2005;Chakrabandhu et al, 2007Chakrabandhu et al, , 2008. We found that Fas internalization in H9 cells ( Figure 6) was similar in efficiency to that documented elsewhere (Piazzolla et al, 2005;Lee et al, 2006;Chakrabandhu et al, 2007). However, deficiency in ezrin did not affect endocytosis of Fas in H9 cells, suggesting that the observed enhanced DISC formation (Figure 7) was not due to altered internalization of Fas.…”

Section: Discussionsupporting

confidence: 69%

“…Internalization of Fas is required for efficient DISC formation and caspase-8 activation (Lee et al, 2006;Chakrabandhu et al, 2007). Ezrin-actin association is reported to be required for endocytosis of Fas in mouse embryonic fibroblasts and L12.10 cells (Piazzolla et al, 2005;Chakrabandhu et al, 2007Chakrabandhu et al, , 2008.…”

Section: Discussionmentioning

confidence: 99%

“…Similar to previous reports (Parlato et al, 2000;Lozupone et al, 2004), recombinant ezrin bound directly to Fas in a glutathione S-transferase (GST) pull-down assay (Figure 1a). The association of ezrin with Fas during the course of Fas-mediated apoptosis was also monitored in H9 cells, a type I cell line known for prominent DISC formation (Scaffidi et al, 1998;Algeciras-Schimnich et al, 2002;Lee et al, 2006). Ezrin was associated with Fas in H9 cells before treatment (Figure 1b).…”

Section: Dissociation Of Ezrin From Death Receptor After Fas Ligand (mentioning

confidence: 96%

“…Normal Fas endocytosis in ezrin-deficient H9 cells after Fas engagement Another reported function of ezrin is its involvement in the endocytosis of Fas that is essential for DISC formation and the activation of caspase-8 (Lee et al, 2006;Chakrabandhu et al, 2007). We analysed whether the internalization of Fas was affected by ezrin deficiency in H9 cells.…”

Section: Deficiency In Ezrin Enhancesmentioning

confidence: 99%

“…Depending on the amount of DISC formation, Fas-sensitive cells are divided into type I and type II (Scaffidi et al, 1998). In type I cells, Fas forms sodium dodecyl sulfate-resistant high-order aggregates, followed by rapid internalization of Fas and DISC formation (Algeciras-Schimnich et al, 2002;Lee et al, 2006;Chakrabandhu et al, 2007;Feig et al, 2007). In type II cells, a very limited amount of DISC is formed and apoptotic signaling needs amplification through mitochondria (Scaffidi et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

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Ezrin is a negative regulator of death receptor-induced apoptosis

et al. 2009

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Ezrin links cortical actin filaments with the cell membrane, and has a critical role in many membrane-initiated events. Fas is directly associated with ezrin, but conflicting results have been reported for the involvement of ezrin in Fas-induced cell death. In this study we show that ezrin was associated with Fas in T cells before stimulation and was released shortly after Fas ligand (FasL) engagement. The knockdown of ezrin moderately increased Fastriggered or tumor necrosis factor-related apoptosisinducing ligand (TRAIL)-triggered cell death in normal T lymphocytes and in H9 cells, but had no effect on death receptor-induced apoptosis in type II cells, such as Jurkat and CEM. Expression of a dominant-negative form of ezrin also led to an increased Fas-induced apoptosis in H9 cells. Ezrin deficiency did not affect the internalization of Fas after Fas ligation. Instead, an enhanced formation of death-inducing signaling complex (DISC) was observed in H9 cells with ezrin knockdown, leading to accelerated caspase-8 activation. Together, our results suggest that ezrin has a negative role in the recruitment of Fas into signaling complexes in type I T cells. Loss of ezrin likely removes the constraint imposed by ezrin and facilitates the assembly of death receptor complex in T cells.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Dissociation Of Ezrin From Death Receptor After Fas Ligand (mentioning

confidence: 96%

Section: Deficiency In Ezrin Enhancesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ezrin is a negative regulator of death receptor-induced apoptosis

et al. 2009

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Death Receptors

Krammer¹,

Lavrik²

2009

Encyclopedia of Life Sciences

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Apoptosis or programmed cell death is a common property of all multicellular organisms. It can be triggered by a number of factors including ultraviolet (UV) or γ‐irradiation, chemotherapeutic drugs or growth factor withdrawal. A death signal can either be induced by death receptors (extrinsic pathway) or via the mitochondria (intrinsic pathway). The death receptor (DR) family is the subfamily of the tumour necrosis factor receptor (TNFR) superfamily. Stimulation of the death receptors results in the transduction of either apoptotic or survival signals. Here we present a general overview of death receptor signalling and describe the main mechanisms leading to activation of death receptor signalling pathways. Key concepts: Stimulation of the death receptors (DR) leads to apoptosis. All DR are distinguished by the presence of the death domain. Crosslinking of DR with death ligands results in formation of the death‐inducing signalling complex (DISC). Caspases play the central role in the transduction of death receptor apoptotic signal. As a result of DISC formation procaspase‐8 is activated with the formation of the active caspase‐8 heterotetramer, which then triggers apoptotic signal. c‐FLIP proteins block caspase‐8 activation at the DISC and thereby death receptor‐induced apoptosis. There are two types of apoptotic signalling: Type I and Type II cells. Stimulation of DR also might lead to the induction of nonapoptotic pathways.

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Death Receptors

Krammer

Pietkiewicz

Lavrik

2016

Encyclopedia of Life Sciences

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Apoptosis, or programmed cell death, is a common property of all multicellular organisms and maintains essential cellular homeostasis in tissues by balancing cell renewal and removal of mutated or old cells. It can be triggered by a number of factors including ultraviolet (UV) or γ‐irradiation, chemotherapeutic drugs or growth factor withdrawal. A death signal can either be induced by the activation of death receptors (DRs, extrinsic pathway) or via the mitochondria (intrinsic pathway). The DR family is a subfamily of the tumour necrosis factor receptor (TNFR) superfamily. Stimulation of the DRs results in the formation of high‐molecular‐weight protein complexes that transduce apoptotic, necroptotic or survival signals. Key Concepts Stimulation of the death receptors (DRs) leads to apoptosis, necroptosis or NF‐κB activation. All DRs are distinguished by the presence of the death domain (DD). Cross‐linking of DR with death ligands results in the formation of the death‐inducing signalling complex (DISC). Caspases play the central role in the transduction of DR‐induced apoptotic signal. Procaspase‐8 is activated at the death effector domain (DED) chains at the DISC. c‐FLIP proteins block or promote caspase‐8 activation at the DISC depending on their amount at the receptor complex and thereby regulate DR‐induced apoptosis. Stimulation of DR might lead to the induction of receptor‐interacting protein kinase 1 and 3 (RIPK1‐ and RIPK3)‐mediated nonapoptotic cell death, necroptosis. Apoptosis and necroptosis are triggered by high‐molecular‐weight protein complexes consisting of similar proteins.

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The role of receptor internalization in CD95 signaling

Cited by 212 publications

References 50 publications

Ezrin is a negative regulator of death receptor-induced apoptosis

Ezrin is a negative regulator of death receptor-induced apoptosis

Death Receptors

Death Receptors

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