Functional characterization of enzymes catalyzing ceramide phosphoethanolamine biosynthesis in mice[S]
Besides bulk amounts of SM, mammalian cells produce small quantities of the SM analog ceramide phosphoethanolamine (CPE). Little is known about the biological role of CPE or enzymes responsible for CPE production. Heterologous expression studies revealed that SM synthase (SMS)2 is a bifunctional enz...
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doaj-b55343a153c440909b926aa8cdb55ae32021-04-28T06:00:21ZengElsevierJournal of Lipid Research0022-22752015-04-01564821835Functional characterization of enzymes catalyzing ceramide phosphoethanolamine biosynthesis in mice[S]Andreas Bickert0Christina Ginkel1Matthijs Kol2Katharina vom Dorp3Holger Jastrow4Joachim Degen5René L. Jacobs6Dennis E. Vance7Elke Winterhager8Xian-Cheng Jiang9Peter Dörmann10Pentti Somerharju11Joost C.M. Holthuis12Klaus Willecke13Molecular Genetics, Life, and Medical Sciences Institute University of Bonn, 53115 Bonn, GermanyMolecular Genetics, Life, and Medical Sciences Institute University of Bonn, 53115 Bonn, GermanyMolecular Cell Biology Division, Department of Biology/Chemistry, University of Osnabrück, 49076 Osnabrück, GermanyInstitute of Molecular Physiology and Biotechnology of Plants, University of Bonn, 53115 Bonn, GermanyImaging Center Essen, Electron Microscopy Unit, University Hospital University of Duisburg-Essen, 45147 Essen, GermanyMolecular Genetics, Life, and Medical Sciences Institute University of Bonn, 53115 Bonn, GermanyDepartments of Agricultural, Food, and Nutritional Science, Molecular and Cell Biology of Lipids, University of Alberta, T6G 2S2 Edmonton, CanadaBiochemistry, University of Alberta, T6G 2S2 Edmonton, CanadaDepartment of Molecular Biology, University of Duisburg-Essen, 45147 Essen, GermanyDepartment of Anatomy and Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY 11203Institute of Molecular Physiology and Biotechnology of Plants, University of Bonn, 53115 Bonn, GermanyMedical Biochemistry, Institute of Biomedicine, University of Helsinki, 00014 Helsinki, FinlandTo whom correspondence should be addressed. (K.W.); (J.C.M.H.); Molecular Cell Biology Division, Department of Biology/Chemistry, University of Osnabrück, 49076 Osnabrück, Germany; To whom correspondence should be addressed. (K.W.); (J.C.M.H.)To whom correspondence should be addressed. (K.W.); (J.C.M.H.); Molecular Genetics, Life, and Medical Sciences Institute University of Bonn, 53115 Bonn, Germany; To whom correspondence should be addressed. (K.W.); (J.C.M.H.)Besides bulk amounts of SM, mammalian cells produce small quantities of the SM analog ceramide phosphoethanolamine (CPE). Little is known about the biological role of CPE or enzymes responsible for CPE production. Heterologous expression studies revealed that SM synthase (SMS)2 is a bifunctional enzyme producing both SM and CPE, whereas SMS-related protein (SMSr) serves as monofunctional CPE synthase. Acute disruption of SMSr catalytic activity in cultured cells causes a rise in endoplasmic reticulum (ER) ceramides, fragmentation of ER exit sites, and induction of mitochondrial apoptosis. To address the relevance of CPE biosynthesis in vivo, we analyzed the tissue-specific distribution of CPE in mice and generated mouse lines lacking SMSr and SMS2 catalytic activity. We found that CPE levels were >300-fold lower than SM in all tissues examined. Unexpectedly, combined inactivation of SMSr and SMS2 significantly reduced, but did not eliminate, tissue-specific CPE pools and had no obvious impact on mouse development or fertility. While SMSr is widely expressed and serves as the principal CPE synthase in the brain, blocking its catalytic activity did not affect ceramide levels or secretory pathway integrity in the brain or any other tissue. Our data provide a first inventory of CPE species and CPE-biosynthetic enzymes in mammals.http://www.sciencedirect.com/science/article/pii/S0022227520355644brain lipidsenzyme inactivationgeneticsmass spectrometrysterile α motif domain-containing protein 8sphingomyelin synthase-related protein |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Andreas Bickert Christina Ginkel Matthijs Kol Katharina vom Dorp Holger Jastrow Joachim Degen René L. Jacobs Dennis E. Vance Elke Winterhager Xian-Cheng Jiang Peter Dörmann Pentti Somerharju Joost C.M. Holthuis Klaus Willecke |
spellingShingle |
Andreas Bickert Christina Ginkel Matthijs Kol Katharina vom Dorp Holger Jastrow Joachim Degen René L. Jacobs Dennis E. Vance Elke Winterhager Xian-Cheng Jiang Peter Dörmann Pentti Somerharju Joost C.M. Holthuis Klaus Willecke Functional characterization of enzymes catalyzing ceramide phosphoethanolamine biosynthesis in mice[S] Journal of Lipid Research brain lipids enzyme inactivation genetics mass spectrometry sterile α motif domain-containing protein 8 sphingomyelin synthase-related protein |
author_facet |
Andreas Bickert Christina Ginkel Matthijs Kol Katharina vom Dorp Holger Jastrow Joachim Degen René L. Jacobs Dennis E. Vance Elke Winterhager Xian-Cheng Jiang Peter Dörmann Pentti Somerharju Joost C.M. Holthuis Klaus Willecke |
author_sort |
Andreas Bickert |
title |
Functional characterization of enzymes catalyzing ceramide phosphoethanolamine biosynthesis in mice[S] |
title_short |
Functional characterization of enzymes catalyzing ceramide phosphoethanolamine biosynthesis in mice[S] |
title_full |
Functional characterization of enzymes catalyzing ceramide phosphoethanolamine biosynthesis in mice[S] |
title_fullStr |
Functional characterization of enzymes catalyzing ceramide phosphoethanolamine biosynthesis in mice[S] |
title_full_unstemmed |
Functional characterization of enzymes catalyzing ceramide phosphoethanolamine biosynthesis in mice[S] |
title_sort |
functional characterization of enzymes catalyzing ceramide phosphoethanolamine biosynthesis in mice[s] |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2015-04-01 |
description |
Besides bulk amounts of SM, mammalian cells produce small quantities of the SM analog ceramide phosphoethanolamine (CPE). Little is known about the biological role of CPE or enzymes responsible for CPE production. Heterologous expression studies revealed that SM synthase (SMS)2 is a bifunctional enzyme producing both SM and CPE, whereas SMS-related protein (SMSr) serves as monofunctional CPE synthase. Acute disruption of SMSr catalytic activity in cultured cells causes a rise in endoplasmic reticulum (ER) ceramides, fragmentation of ER exit sites, and induction of mitochondrial apoptosis. To address the relevance of CPE biosynthesis in vivo, we analyzed the tissue-specific distribution of CPE in mice and generated mouse lines lacking SMSr and SMS2 catalytic activity. We found that CPE levels were >300-fold lower than SM in all tissues examined. Unexpectedly, combined inactivation of SMSr and SMS2 significantly reduced, but did not eliminate, tissue-specific CPE pools and had no obvious impact on mouse development or fertility. While SMSr is widely expressed and serves as the principal CPE synthase in the brain, blocking its catalytic activity did not affect ceramide levels or secretory pathway integrity in the brain or any other tissue. Our data provide a first inventory of CPE species and CPE-biosynthetic enzymes in mammals. |
topic |
brain lipids enzyme inactivation genetics mass spectrometry sterile α motif domain-containing protein 8 sphingomyelin synthase-related protein |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520355644 |
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