2025
Suppression of endothelial ceramide de novo biosynthesis by Nogo-B contributes to cardiometabolic diseases
Rubinelli L, Manzo O, Sungho J, Del Gaudio I, Bareja R, Marino A, Palikhe S, Di Mauro V, Bucci M, Falcone D, Elemento O, Ersoy B, Diano S, Sasset L, Di Lorenzo A. Suppression of endothelial ceramide de novo biosynthesis by Nogo-B contributes to cardiometabolic diseases. Nature Communications 2025, 16: 1968. PMID: 40000621, PMCID: PMC11862206, DOI: 10.1038/s41467-025-56869-9.Peer-Reviewed Original ResearchConceptsNogo-BEndothelial dysfunctionHFD miceCardiometabolic diseasesSphingolipid signalingDevelopment of therapeutic strategiesBioactive sphingolipidsCeramide degradationSphingosine-1-phosphateHepatic glucose productionIn vivo evidenceEndothelial cellsEndothelial specific deletionCeramideBiosynthesisHigh-fat dietPathological implicationsSphingolipidsGlucose productionHFDIn vivoMale miceMetabolic dysfunctionTherapeutic strategiesMetabolic disorders
2022
Pathogenic variants of sphingomyelin synthase SMS2 disrupt lipid landscapes in the secretory pathway
Sokoya T, Parolek J, Foged M, Danylchuk D, Bozan M, Sarkar B, Hilderink A, Philippi M, Botto L, Terhal P, Mäkitie O, Piehler J, Kim Y, Burd C, Klymchenko A, Maeda K, Holthuis J. Pathogenic variants of sphingomyelin synthase SMS2 disrupt lipid landscapes in the secretory pathway. ELife 2022, 11: e79278. PMID: 36102623, PMCID: PMC9531943, DOI: 10.7554/elife.79278.Peer-Reviewed Original ResearchConceptsSecretory pathwayER export signalPatient-derived fibroblastsFull enzymatic activityPhysical membrane propertiesExport signalSterol gradientLipid landscapeMammalian cellsCholesterol organizationLipid orderEnzymatic activityLipid distributionOsteogenic cellsPathwayBone phenotypeSMS2Glycerophospholipid profilePathogenic variantsCellsVariantsSphingomyelinSkeletal dysplasiaERSphingolipids
2021
CD1a selectively captures endogenous cellular lipids that broadly block T cell response
Cotton R, Wegrecki M, Cheng T, Chen Y, Veerapen N, Le Nours J, Orgill D, Pomahac B, Talbot S, Willis R, Altman J, de Jong A, Van Rhijn I, Clark R, Besra G, Ogg G, Rossjohn J, Moody D. CD1a selectively captures endogenous cellular lipids that broadly block T cell response. Journal Of Experimental Medicine 2021, 218: e20202699. PMID: 33961028, PMCID: PMC8111460, DOI: 10.1084/jem.20202699.Peer-Reviewed Original ResearchConceptsNatural endogenous inhibitorsEndogenous lipidsCD1a proteinCellular lipidsT cell activationMembrane phospholipidsLonger lipidsSurface residuesEndogenous inhibitorLipidomics methodDetailed chemical structureCell activationLipidsCellsNatural blockerSphingolipidsDisplay platformProteinCrystal structureResiduesCell responsesBindingTetramerC42Sphingomyelin
2019
Lipid‐dependent coupling of secretory cargo sorting and trafficking at the trans‐Golgi network
von Blume J, Hausser A. Lipid‐dependent coupling of secretory cargo sorting and trafficking at the trans‐Golgi network. FEBS Letters 2019, 593: 2412-2427. PMID: 31344259, PMCID: PMC8048779, DOI: 10.1002/1873-3468.13552.Peer-Reviewed Original Research
2013
Sphingolipid Homeostasis in the Endoplasmic Reticulum and Beyond
Breslow DK. Sphingolipid Homeostasis in the Endoplasmic Reticulum and Beyond. Cold Spring Harbor Perspectives In Biology 2013, 5: a013326. PMID: 23545423, PMCID: PMC3683901, DOI: 10.1101/cshperspect.a013326.BooksConceptsSphingolipid homeostasisEndoplasmic reticulumEssential cellular rolesSphingolipid metabolismCritical regulatory sitePotent signaling moleculesCellular rolesFamily proteinsSphingolipid productionSignaling moleculesRegulatory sitesPhysiologic cuesBasic biochemistryComplex glycosphingolipidsMembrane functionHomeostasisDiverse groupSphingolipidsNew insightsReticulumMetabolic demandsDetailed understandingMetabolismStructural componentsInitial synthesis
2010
Membranes in Balance: Mechanisms of Sphingolipid Homeostasis
Breslow DK, Weissman JS. Membranes in Balance: Mechanisms of Sphingolipid Homeostasis. Molecular Cell 2010, 40: 267-279. PMID: 20965421, PMCID: PMC2987644, DOI: 10.1016/j.molcel.2010.10.005.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsSphingolipid homeostasisCell biologyEukaryotic cell biologyKey cellular rolesComplex membrane compositionCellular rolesSecretory pathwaySphingolipid biosynthesisEnzymatic machineryPhysiologic cuesSphingolipid metabolismMembrane compositionSphingolipidsBiologyNew insightsHomeostasisStructural componentsMembraneCellsBiosynthesisDefining featureMachineryGlycerolipidsEnzymeImproved understanding
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