Ceramide phosphoethanolamine synthase SMSr is a target of caspase-6 during apoptotic cell death
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https://osnadocs.ub.uni-osnabrueck.de/handle/urn:nbn:de:gbv:700-2018010516506
https://osnadocs.ub.uni-osnabrueck.de/handle/urn:nbn:de:gbv:700-2018010516506
Title: | Ceramide phosphoethanolamine synthase SMSr is a target of caspase-6 during apoptotic cell death |
Authors: | Cabukusta, Birol Nettebrock, Niclas T. Kol, Matthijs Hilderink, Angelika Tafesse, Fikadu G. Holthuis, Joost C. M. |
Abstract: | Ceramides are essential precursors of sphingolipids with a dual role as mediators of apoptotic cell death. Previous work revealed that the ER-resident ceramide phosphoethanolamine (CPE) synthase SMSr/SAMD8 is a suppressor of ceramide-mediated apoptosis in cultured cells. Anti-apoptotic activity of SMSr requires a catalytically active enzyme but also relies on the enzyme’s N-terminal sterile α-motif or SAM domain. Here, we demonstrate that SMSr itself is a target of the apoptotic machinery. Treatment of cells with staurosporine or the death receptor ligand FasL triggers caspase-mediated cleavage of SMSr at a conserved aspartate located downstream of the enzyme’s SAM domain and upstream of its first membrane span. Taking advantage of reconstitution experiments with SMSr produced in a cell-free expression system, specific caspase-inhibitors and gene silencing approaches, we show that SMSr is a novel and specific substrate of caspase-6, a non-conventional effector caspase implicated in Huntington’s and Alzheimer’s diseases. Our findings underscore a role of SMSr as negative regulator of ceramide-induced cell death and, in view of a prominent expression of the enzyme in brain, raise questions regarding its potential involvement in neurodegenerative disorders. |
Citations: | Bioscience Reports 37(4) 2017 |
URL: | https://osnadocs.ub.uni-osnabrueck.de/handle/urn:nbn:de:gbv:700-2018010516506 |
Subject Keywords: | aptoptosis; caspases; membrane biochemistry; sphingolipids |
Issue Date: | 5-Jan-2018 |
License name: | Namensnennung 4.0 International |
License url: | http://creativecommons.org/licenses/by/4.0/ |
Type of publication: | Einzelbeitrag in einer wissenschaftlichen Zeitschrift [article] |
Appears in Collections: | FB05 - Hochschulschriften Open-Access-Publikationsfonds |
Files in This Item:
File | Description | Size | Format | |
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Artikel_Bioscience_Reports_37_2017_Holthuis.pdf | 1,18 MB | Adobe PDF | Artikel_Bioscience_Reports_37_2017_Holthuis.pdf View/Open |
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