2018
Glutamine metabolism via glutaminase 1 in autosomal-dominant polycystic kidney disease
Soomro I, Sun Y, Li Z, Diggs L, Hatzivassiliou G, Thomas AG, Rais R, Parker SJ, Slusher BS, Kimmelman AC, Somlo S, Skolnik EY. Glutamine metabolism via glutaminase 1 in autosomal-dominant polycystic kidney disease. Nephrology Dialysis Transplantation 2018, 33: 1343-1353. PMID: 29420817, PMCID: PMC6070111, DOI: 10.1093/ndt/gfx349.Peer-Reviewed Original ResearchConceptsCyst growthCB-839Mouse modelGlutaminase 1Glutamine metabolismAutosomal dominant polycystic kidney disease cellsAutosomal dominant polycystic kidney diseaseCyst-lining epithelial cellsNormal human kidneyCompensatory metabolic changesInhibited mammalian targetPolycystic kidney diseaseCyst-lining epitheliaTumor cell proliferationKidney diseaseAnimal modelsGLS1 inhibitionHuman ADPKD kidneysHuman kidneyMammalian targetVariable outcomesCyst formationMetabolic changesADPKDMetabolism of glutamine
2015
Essential Role of X-Box Binding Protein-1 during Endoplasmic Reticulum Stress in Podocytes
Hassan H, Tian X, Inoue K, Chai N, Liu C, Soda K, Moeckel G, Tufro A, Lee AH, Somlo S, Fedeles S, Ishibe S. Essential Role of X-Box Binding Protein-1 during Endoplasmic Reticulum Stress in Podocytes. Journal Of The American Society Of Nephrology 2015, 27: 1055-1065. PMID: 26303067, PMCID: PMC4814187, DOI: 10.1681/asn.2015020191.Peer-Reviewed Original ResearchConceptsX-box binding protein 1Endoplasmic reticulum stress responseEndoplasmic reticulum stressGlomerular filtration barrierPodocyte injuryReticulum stress responseBinding protein 1Reticulum stressProtein 1Filtration barrierFoot process effacementProgressive albuminuriaMouse modelProcess effacementUnfolded protein response pathwayEpithelial cellsNormal glomerular filtration barrierProtein response pathwayEndoplasmic reticulumPodocytesGenetic inactivationXBP1 pathwayInjuryJNK pathwayStress responsePolycystin-1 Is a Cardiomyocyte Mechanosensor That Governs L-Type Ca2+ Channel Protein Stability
Pedrozo Z, Criollo A, Battiprolu PK, Morales CR, Contreras-Ferrat A, Fernández C, Jiang N, Luo X, Caplan MJ, Somlo S, Rothermel BA, Gillette TG, Lavandero S, Hill JA. Polycystin-1 Is a Cardiomyocyte Mechanosensor That Governs L-Type Ca2+ Channel Protein Stability. Circulation 2015, 131: 2131-2142. PMID: 25888683, PMCID: PMC4470854, DOI: 10.1161/circulationaha.114.013537.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBiomarkersCalcium Channels, L-TypeCardiomegalyCells, CulturedFibrosisHypertrophyHypotonic SolutionsMaleMechanotransduction, CellularMiceMice, KnockoutMyocytes, CardiacProtein Interaction MappingProtein StabilityProtein Structure, TertiaryRatsRats, Sprague-DawleyRecombinant Fusion ProteinsRNA InterferenceStress, MechanicalTRPP Cation ChannelsConceptsL-type calcium channel activityCalcium channel activityNeonatal rat ventricular myocytesRat ventricular myocytesKnockout miceVentricular myocytesChannel activityMechanical stretchNeonatal rat ventricular myocyte hypertrophyProtein levelsVentricular myocyte hypertrophyL-type Ca2G protein-coupled receptor-like proteinPolycystin-1Channel protein levelsCyclic mechanical stretchControl miceInterstitial fibrosisStress-induced activationCardiac massMechanical stress-induced activationCardiac functionRNAi-dependent knockdownCardiac hypertrophyLittermate controls
2014
N-Glycosylation Determines the Abundance of the Transient Receptor Potential Channel TRPP2*
Hofherr A, Wagner C, Fedeles S, Somlo S, Köttgen M. N-Glycosylation Determines the Abundance of the Transient Receptor Potential Channel TRPP2*. Journal Of Biological Chemistry 2014, 289: 14854-14867. PMID: 24719335, PMCID: PMC4031537, DOI: 10.1074/jbc.m114.562264.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAsparagineBinding SitesBlotting, WesternCell LineCells, CulturedGlucosidasesGlycosylationHEK293 CellsHeLa CellsHumansIntracellular Signaling Peptides and ProteinsLysosomesMass SpectrometryMiceMice, KnockoutMicroscopy, FluorescenceMutationPolycystic Kidney, Autosomal DominantProtein Serine-Threonine KinasesProteolysisPyruvate Dehydrogenase Acetyl-Transferring KinaseConceptsGlucosidase IINon-catalytic β-subunitsProtein expressionFirst extracellular loopAutosomal dominant polycystic liver diseaseEfficient biogenesisGenetic interactionsMembrane proteinsBiochemical approachesN-glycosylationGenetic approachesTRPP2Glycosylation sitesBiological roleLysosomal degradationΒ-subunitChemical inhibitionBiogenesisExtracellular loopNonselective cation channelsIon channelsBiological importanceGlycosylationCation channelsProtein levels