A search for ceramide binding proteins using bifunctional lipid analogs yields CERT-related protein StarD7

DC FieldValueLanguage
dc.contributor.authorBockelmann, Svenja
dc.contributor.authorMina, John G. M.
dc.contributor.authorKorneev, Sergei
dc.contributor.authorHassan, Dina G.
dc.contributor.authorMueller, Dagmar
dc.contributor.authorHilderink, Angelika
dc.contributor.authorVlieg, Hedwich C.
dc.contributor.authorRaijmakers, Reinout
dc.contributor.authorHeck, Albert J. R.
dc.contributor.authorHaberkant, Per
dc.contributor.authorHolthuis, Joost C. M.
dc.date.accessioned2021-12-23T16:18:58Z-
dc.date.available2021-12-23T16:18:58Z-
dc.date.issued2018
dc.identifier.issn00222275
dc.identifier.urihttps://osnascholar.ub.uni-osnabrueck.de/handle/unios/12933-
dc.description.abstractCeramides are central intermediates of sphingolipid metabolism with dual roles as mediators of cellular stress signaling and mitochondrial apoptosis. How ceramides exert their cytotoxic effects is unclear and their poor solubility in water hampers a search for specific protein interaction partners. Here, we report the application of a photoactivatable and clickable ceramide analog, pacCer, to identify ceramide binding proteins and unravel the structural basis by which these proteins recognize ceramide. Besides capturing ceramide transfer protein (CERT) from a complex proteome, our approach yielded CERT-related steroidogenic acute regulatory protein D7 (StarD7) as novel ceramide binding protein. Previous work revealed that StarD7 is required for efficient mitochondrial import of phosphatidylcholine (PC) and serves a critical role in mitochondrial function and morphology. Combining site-directed mutagenesis and photoaffinity labeling experiments, we demonstrate that the steroidogenic acute regulatory transfer domain of StarD7 harbors a common binding site for PC and ceramide. While StarD7 lacks robust ceramide transfer activity in vitro, we find that its ability to shuttle PC between model membranes is specifically affected by ceramides. Besides demonstrating the suitability of pacCer as a tool to hunt for ceramide binding proteins, our data point at StarD7 as a candidate effector protein by which ceramides may exert part of their mitochondria- mediated cytotoxic effects.
dc.description.sponsorshipMarie Curie Intra-European FellowshipEuropean Commission; European Commission Seventh Framework ProgrammeEuropean Commission [289278]; Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [SFB944-P14]; Netherlands Organisation for Scientific ResearchNetherlands Organization for Scientific Research (NWO) [184.032.201]; Netherlands Proteomics Centre; This work was supported by a Marie Curie Intra-European Fellowship (to J.G.M.M.), European Commission Seventh Framework Programme (Marie-Curie ITN ``Sphingonet'') Grant 289278, and Deutsche Forschungsgemeinschaft Grant SFB944-P14 (to J.C.M.H.). Additional support was provided by Netherlands Organisation for Scientific Research Grant 184.032.201, through the funding of the large-scale proteomics facility, Proteins@Work, embedded in the Netherlands Proteomics Centre. The authors declare that they have no conflicts of interest with the contents of this article.
dc.language.isoen
dc.publisherAMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
dc.relation.ispartofJOURNAL OF LIPID RESEARCH
dc.subjectBiochemistry & Molecular Biology
dc.subjectCELLS
dc.subjectceramide transfer protein
dc.subjectCHOLESTEROL
dc.subjectclick chemistry
dc.subjectEADOCK DSS
dc.subjectIDENTIFICATION
dc.subjectINDUCED APOPTOSIS
dc.subjectlipid transfer protein
dc.subjectmitochondria
dc.subjectMITOCHONDRIAL OUTER-MEMBRANE
dc.subjectNONVESICULAR TRAFFICKING
dc.subjectphosphatidylcholine
dc.subjectPHOSPHATIDYLCHOLINE TRANSFER PROTEIN
dc.subjectphotoaffinity labeling
dc.subjectsteroidogenic acute regulatory protein D7
dc.subjectSWISS-MODEL
dc.subjectTRANSMEMBRANE DOMAIN
dc.titleA search for ceramide binding proteins using bifunctional lipid analogs yields CERT-related protein StarD7
dc.typejournal article
dc.identifier.doi10.1194/jlr.M082354
dc.identifier.isiISI:000426357600011
dc.description.volume59
dc.description.issue3
dc.description.startpage515
dc.description.endpage530
dc.contributor.orcid0000-0003-0429-1370
dc.contributor.orcid0000-0002-2405-4404
dc.contributor.orcid0000-0002-2754-015X
dc.contributor.orcid0000-0001-8912-1586
dc.contributor.orcid0000-0001-6316-6663
dc.contributor.researcheridN-8622-2014
dc.contributor.researcheridAAG-2675-2021
dc.contributor.researcheridAAL-9157-2020
dc.contributor.researcheridAAX-9374-2021
dc.contributor.researcheridD-7098-2011
dc.contributor.researcheridA-3045-2010
dc.identifier.eissn15397262
dc.publisher.place11200 ROCKVILLE PIKE, SUITE 302, ROCKVILLE, MD, UNITED STATES
dcterms.isPartOf.abbreviationJ. Lipid Res.
dcterms.oaStatusGreen Published, hybrid
crisitem.author.deptFB 05 - Biologie/Chemie-
crisitem.author.deptFB 05 - Biologie/Chemie-
crisitem.author.deptidfb05-
crisitem.author.deptidfb05-
crisitem.author.parentorgUniversität Osnabrück-
crisitem.author.parentorgUniversität Osnabrück-
crisitem.author.netidBoSv426-
crisitem.author.netidKoSe681-
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