Raft component GD3 associates with tubulin following CD95/Fas ligation

Sorice, Maurizio; Matarrese, Paola; Tinari, Antonella; Giammarioli, Anna Maria; Garofalo, Tina; Manganelli, Valeria; Ciarlo, Laura; Gambardella, Lucrezia; Maccari, Giorgio; Botta, Maurizio; Misasi, Roberta; Malorni, Walter

doi:10.1096/fj.08-128140

Cited by 37 publications

(36 citation statements)

References 48 publications

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“…Finally, a recent work also suggested that sphingolipids could act as regulators of the crosstalk between apoptosis and autophagy. 33 In the present work, in agreement with these observations, [15][16][17][18] and with those underlying the presence of GD3 not only on the plasma membrane, but also in the cell cytoplasm, 34,35 including the ER-mitochondria associated membranes, 36 we found that the inhibitor of ceramide synthase FB1 significantly prevented autophagy induced either by amino acid starvation or by tunicamycin. Furthermore, we point out a specific role for ganglioside GD3, since we found that the knocking down of GD3 synthase significantly hindered autophagy.…”

Section: Figure 7 Gd3 Associates With Lc3 and Lamp1 Coimmunoprecipisupporting

confidence: 92%

Evidence for the involvement of GD3 ganglioside in autophagosome formation and maturation

et al. 2014

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Section: Figure 7 Gd3 Associates With Lc3 and Lamp1 Coimmunoprecipisupporting

confidence: 92%

Evidence for the involvement of GD3 ganglioside in autophagosome formation and maturation

et al. 2014

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“…However, the role of lipid rafts in death execution seems to be not merely limited to the plasma membrane, as a role for microdomains has also been observed in the propagation of death stimuli. After the pioneering studies by the group of De Maria 21,22 suggesting an intracellular trafficking of glycosphingolipids, we have shown that (i) the cytoplasmic trafficking of ganglioside GD3, considered as a paradigmatic component of glycosphingolipid microdomains, could occur through its association with cytoskeletal components 28 and (ii) mitochondrial fission-associated proteins are recruited to 'raft-like' lipid microdomains under proapoptotic stimulation. 20 Hence, the data presented here seem to add a novel role for these lipid microdomains, which could contribute to mitochondria remodeling that precedes apoptosis execution.…”

Section: Discussionmentioning

confidence: 99%

Association of fission proteins with mitochondrial raft-like domains

et al. 2010

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It was shown that receptor-mediated apoptosis involves a cascade of subcellular events including alterations of mitochondria. Loss of mitochondrial membrane potential that follows death receptor ligation allows the release of apoptogenic factors that result in apoptosis execution. Further important mitochondrial changes have been observed in this regard: mitochondrial remodeling and fission that appear as prerequisites for the occurrence of the cell death program. As it was observed that lipid rafts, glycosphingolipid-enriched structures, can participate in the apoptotic cascade being recruited to the mitochondria under receptor-mediated proapoptotic stimulation, we decided to analyze the possible implication of these microdomains in mitochondrial fission. We found that molecules involved in mitochondrial fission processes are associated with these domains. In particular, although hFis1 was constitutively included in mitochondrial raft-like domains, dynamin-like protein 1 was recruited to these domains on CD95/Fas triggering. Accordingly, the disruption of rafts, for example, by inhibiting ceramide synthase, leads to the impairment of fission molecule recruitment to the mitochondria, reduction of mitochondrial fission and a significant reduction of apoptosis. We hypothesize that under apoptotic stimulation the recruitment of fission-associated molecules to the mitochondrial rafts could have a role in the morphogenetic changes leading to organelle fission. Maintenance of shape and morphology is required for normal mitochondrial and cellular functions. Mitochondria frequently undergo fission and fusion processes that regulate their morphology, number and function.1,2 This remodeling is of great relevance in both cell life and death being a mitochondrial network involved in all the main cell activities, including proliferation, differentiation and senescence, as well as cell death by apoptosis. In particular, although mitochondrial fusion processes seem to be associated with cell differentiation and senescence, 3 fission processes are mandatory during cell proliferation and, as recently stated, in apoptotic events. Although mitochondrial fusion serves to maintain a tubular mitochondrial network and optimal mitochondrial function, mitochondrial fission is required in dividing cells to ensure inheritance of mitochondria by daughter cells, but it is also important during differentiation in response to new energy demands. 4 Mitochondrial fission and fusion depend on the balance among several fusion and fission proteins. These include mitofusin 1 and 2 (Mfn1, Mfn2) and OPA1, which are large GTPases essential for fusion processes and localized in the mitochondria, associated with the outer (Mfn1 and 2) or inner (OPA1) membrane. [5][6][7] On the fission side, other proteins are involved: dynamin-related protein 1, also known as dynamin-like protein 1 (DLP1), which appears to be recruited to mitochondria to mediate fission activities, 8,9 and the human homologue of mitochondrial fission protein previously found in yeast, t...

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“…We applied fluorescence resonance energy transfer (FRET) analysis by flow cytometry to study the colocalization of GHCer and TRAX (17). Briefly, cells were incubated with various amount of GHCer for 5 minutes at 37 C then fixed and permeabilized, washed twice in cold PBS, and then labeled with antibodies tagged with donor (PE) or acceptor (Cy5) dyes.…”

Section: Fluorescence Resonance Energy Transfermentioning

confidence: 99%

Globo-H Ceramide Shed from Cancer Cells Triggers Translin-Associated Factor X-Dependent Angiogenesis

et al. 2014

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Tumor angiogenesis is a critical element of cancer progression, and strategies for its selective blockade are still sought. Here, we examine the angiogenic effects of Globo-H ceramide (GHCer), the most prevalent glycolipid in a majority of epithelial cancers and one that acts as an immune checkpoint. Here, we report that GHCer becomes incorporated into endothelial cells through the absorption of microvesicles shed from tumor cells. In endothelial cells, GHCer addition induces migration, tube formation, and intracellular Ca 2þ mobilization in vitro and angiogenesis in vivo. Breast cancer cells expressing high levels of GHCer displayed relatively greater tumorigenicity and angiogenesis compared with cells expressing low levels of Globo-H. Clincally, GHCer þ breast cancer specimens contained higher vessel density than GHCer À breast cancer specimens. Mechanistic investigations linked the angiogenic effects of GHCer to its endocytosis and binding to TRAX, with consequent release of PLCb1 from TRAX to trigger Ca 2þ mobilization. Together, our findings highlight the importance of GHC as a target for cancer therapy by providing new information on its key role in tumor angiogenesis. Cancer Res; 74(23); 6856-66. Ó2014 AACR.

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Raft component GD3 associates with tubulin following CD95/Fas ligation

Cited by 37 publications

References 48 publications

Evidence for the involvement of GD3 ganglioside in autophagosome formation and maturation

Evidence for the involvement of GD3 ganglioside in autophagosome formation and maturation

Association of fission proteins with mitochondrial raft-like domains

Globo-H Ceramide Shed from Cancer Cells Triggers Translin-Associated Factor X-Dependent Angiogenesis

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