Functional characterization of enzymes catalyzing ceramide phosphoethanolamine biosynthesis in mice

DC FieldValueLanguage
dc.contributor.authorBickert, Andreas
dc.contributor.authorGinkel, Christina
dc.contributor.authorKol, Matthijs
dc.contributor.authorvom Dorp, Katharina
dc.contributor.authorJastrow, Holger
dc.contributor.authorDegen, Joachim
dc.contributor.authorJacobs, Rene L.
dc.contributor.authorVance, Dennis E.
dc.contributor.authorWinterhager, Elke
dc.contributor.authorJiang, Xian-Cheng
dc.contributor.authorDoermann, Peter
dc.contributor.authorSomerharju, Pentti
dc.contributor.authorHolthuis, Joost C. M.
dc.contributor.authorWillecke, Klaus
dc.date.accessioned2021-12-23T16:22:52Z-
dc.date.available2021-12-23T16:22:52Z-
dc.date.issued2015
dc.identifier.issn00222275
dc.identifier.urihttps://osnascholar.ub.uni-osnabrueck.de/handle/unios/14336-
dc.description.abstractBesides 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.
dc.description.sponsorshipGerman Research Foundation through the Collaborative Research Centre [SFB-645, SFB-944]; European UnionEuropean Commission; Canadian Institutes of Health ResearchCanadian Institutes of Health Research (CIHR) [MOP5182]; [Wi774/22-1]; This study was supported by the German Research Foundation through the Collaborative Research Centre SFB-645, projects B2 to K.W. and Z4 to P.D. and SFB-944 project P14 to J.C.M.H. and by the grant Wi774/22-1 to E.W. and the European Union through the 7th FP Marie-Curie ITN ``Sphingonet'' to J.C.M.H., and the grant MOP5182 from the Canadian Institutes of Health Research to R.L.J. and D.E.V.
dc.language.isoen
dc.publisherAMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
dc.relation.ispartofJOURNAL OF LIPID RESEARCH
dc.subjectAPOPTOSIS
dc.subjectBiochemistry & Molecular Biology
dc.subjectbrain lipids
dc.subjectCELLS
dc.subjectenzyme inactivation
dc.subjectEXPRESSION
dc.subjectgenetics
dc.subjectHOMEOSTASIS
dc.subjectmass spectrometry
dc.subjectMEMBRANE SPHINGOMYELIN
dc.subjectPLASMA
dc.subjectPROTEIN SMSR
dc.subjectRAT-LIVER
dc.subjectSMS2 DEFICIENCY
dc.subjectsphingolipids
dc.subjectsphingomyelin synthase
dc.subjectSPHINGOMYELIN SYNTHASE 2
dc.subjectsphingomyelin synthase-related protein
dc.subjectsterile alpha motif domain-containing protein 8
dc.subjecttransgenic mice
dc.titleFunctional characterization of enzymes catalyzing ceramide phosphoethanolamine biosynthesis in mice
dc.typejournal article
dc.identifier.doi10.1194/jlr.M055269
dc.identifier.isiISI:000351940700006
dc.description.volume56
dc.description.issue4
dc.description.startpage821
dc.description.endpage835
dc.contributor.orcid0000-0002-5525-1355
dc.contributor.orcid0000-0001-8912-1586
dc.contributor.researcheridAAL-9157-2020
dc.identifier.eissn15397262
dc.publisher.place9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
dcterms.isPartOf.abbreviationJ. Lipid Res.
dcterms.oaStatusGreen Published, hybrid
Show simple item record

Page view(s)

3
Last Week
1
Last month
0
checked on Jul 25, 2024

Google ScholarTM

Check

Altmetric