Apoptotic signalling targets the post-endocytic sorting machinery of the death receptor Fas/CD95.

Autor: Sharma S; Department of Biomedical Science & Centre of Membrane Interactions and Dynamics, University of Sheffield, Sheffield, S10 2TN, UK., Carmona A; Department of Biomedical Science & Centre of Membrane Interactions and Dynamics, University of Sheffield, Sheffield, S10 2TN, UK., Skowronek A; Department of Biomedical Science & Centre of Membrane Interactions and Dynamics, University of Sheffield, Sheffield, S10 2TN, UK., Yu F; Department of Biomedical Science & Centre of Membrane Interactions and Dynamics, University of Sheffield, Sheffield, S10 2TN, UK.; Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA., Collins MO; Department of Biomedical Science & Centre of Membrane Interactions and Dynamics, University of Sheffield, Sheffield, S10 2TN, UK., Naik S; Department of Biomedical Science & Centre of Membrane Interactions and Dynamics, University of Sheffield, Sheffield, S10 2TN, UK., Murzeau CM; Department of Biomedical Science & Centre of Membrane Interactions and Dynamics, University of Sheffield, Sheffield, S10 2TN, UK., Tseng PL; Department of Biomedical Science & Centre of Membrane Interactions and Dynamics, University of Sheffield, Sheffield, S10 2TN, UK., Erdmann KS; Department of Biomedical Science & Centre of Membrane Interactions and Dynamics, University of Sheffield, Sheffield, S10 2TN, UK. k.erdmann@sheffield.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2019 Jul 15; Vol. 10 (1), pp. 3105. Date of Electronic Publication: 2019 Jul 15.
DOI: 10.1038/s41467-019-11025-y
Abstrakt: 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.
Databáze: MEDLINE
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