Apoptotic signalling targets the post-endocytic sorting machinery of the death receptor Fas/CD95
| Autor: | Fangyan Yu, Mark O. Collins, Kai S. Erdmann, Claire M. Murzeau, Pei-Li Tseng, Shruti Sharma, Antonio Carmona, Sindhu Naik, Agnieszka Skowronek |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cell death Cell type Fas Ligand Protein Endosome Science Endocytic cycle Regulator Protein Tyrosine Phosphatase Non-Receptor Type 13 Vesicular Transport Proteins General Physics and Astronomy Apoptosis 02 engineering and technology Endosomes General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Antigens Neoplasm Humans fas Receptor lcsh:Science Multidisciplinary Chemistry Dysbindin Intracellular Signaling Peptides and Proteins General Chemistry 021001 nanoscience & nanotechnology Fas receptor Endocytosis Cell biology 030104 developmental biology Cancer cell lcsh:Q Signal transduction 0210 nano-technology Lysosomes HeLa Cells Signal Transduction |
| Zdroj: | Nature Communications Nature Communications, Vol 10, Iss 1, Pp 1-16 (2019) |
| ISSN: | 2041-1723 |
| Popis: | Fas plays a major role in regulating ligand-induced apoptosis in many cell types. It is well known that several cancers demonstrate reduced cell surface levels of Fas and thus escape a potential control system via ligand-induced apoptosis, although underlying mechanisms are unclear. Here we report that the endosome associated trafficking regulator 1 (ENTR1), controls cell surface levels of Fas and Fas-mediated apoptotic signalling. ENTR1 regulates, via binding to the coiled coil domain protein Dysbindin, the delivery of Fas from endosomes to lysosomes thereby controlling termination of Fas signal transduction. We demonstrate that ENTR1 is cleaved during Fas-induced apoptosis in a caspase-dependent manner revealing an unexpected interplay of apoptotic signalling and regulation of endolysosomal trafficking resulting in a positive feedback signalling-loop. Our data provide insights into the molecular mechanism of Fas post-endocytic trafficking and signalling, opening possible explanations on how cancer cells regulate cell surface levels of death receptors. Fas is a death receptor that regulates apoptosis in many cell types and is downregulated on the cell surface in many cancers. Here, Sharma et al. show that endosome associated trafficking regulator ENTR1 regulates delivery of Fas to lysosomes, thereby controlling its degradation and signalling. |
| Databáze: | OpenAIRE |
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