Brandenburg, Sören

[["dc.bibliographiccitation.firstpage","681"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Circulation"],["dc.bibliographiccitation.lastpage","693"],["dc.bibliographiccitation.volume","140"],["dc.contributor.author","Alsina, Katherina M."],["dc.contributor.author","Hulsurkar, Mohit"],["dc.contributor.author","Brandenburg, Sören"],["dc.contributor.author","Kownatzki-Danger, Daniel"],["dc.contributor.author","Lenz, Christof"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Abu-Taha, Issam"],["dc.contributor.author","Kamler, Markus"],["dc.contributor.author","Chiang, David Y."],["dc.contributor.author","Lahiri, Satadru K."],["dc.contributor.author","Reynolds, Julia O."],["dc.contributor.author","Quick, Ann P."],["dc.contributor.author","Scott, Larry"],["dc.contributor.author","Word, Tarah A."],["dc.contributor.author","Gelves, Maria D."],["dc.contributor.author","Heck, Albert J.R."],["dc.contributor.author","Li, Na"],["dc.contributor.author","Dobrev, Dobromir"],["dc.contributor.author","Lehnart, Stephan E."],["dc.contributor.author","Wehrens, Xander H.T."],["dc.date.accessioned","2020-12-10T18:38:03Z"],["dc.date.available","2020-12-10T18:38:03Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1161/CIRCULATIONAHA.119.039642"],["dc.identifier.pmid","31185731"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77173"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/203"],["dc.identifier.url","https://sfb1190.med.uni-goettingen.de/production/literature/publications/133"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | S02: Hochauflösende Fluoreszenzmikroskopie und integrative Datenanalyse"],["dc.relation","SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente"],["dc.relation","SFB 1190 | P03: Erhaltung und funktionelle Kopplung von ER-Kontakten mit der Plasmamembran"],["dc.relation.workinggroup","RG Lehnart"],["dc.relation.workinggroup","RG Brandenburg"],["dc.relation.workinggroup","RG Lenz"],["dc.title","Loss of Protein Phosphatase 1 Regulatory Subunit PPP1R3A Promotes Atrial Fibrillation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Circulation Research"],["dc.bibliographiccitation.volume","128"],["dc.contributor.author","Peper, Jonas"],["dc.contributor.author","Kownatzki-Danger, Daniel"],["dc.contributor.author","Weninger, Gunnar"],["dc.contributor.author","Seibertz, Fitzwilliam"],["dc.contributor.author","Pronto, Julius Ryan D."],["dc.contributor.author","Sutanto, Henry"],["dc.contributor.author","Pacheu-Grau, David"],["dc.contributor.author","Hindmarsh, Robin"],["dc.contributor.author","Brandenburg, Sören"],["dc.contributor.author","Lehnart, Stephan E."],["dc.date.accessioned","2021-06-01T09:42:10Z"],["dc.date.available","2021-06-01T09:42:10Z"],["dc.date.issued","2021"],["dc.description.abstract","Rationale: CAV3 (caveolin3) variants associated with arrhythmogenic cardiomyopathy and muscular dystrophy can disrupt post-Golgi surface trafficking. As CAV1 (caveolin1) was recently identified in cardiomyocytes, we hypothesize that conserved isoform-specific protein/protein interactions orchestrate unique cardiomyocyte microdomain functions. To analyze the CAV1 versus CAV3 interactome, we employed unbiased live-cell proximity proteomic, isoform-specific affinity, and complexome profiling mass spectrometry techniques. We demonstrate the physiological relevance and loss-of-function mechanism of a novel CAV3 interactor in gene-edited human induced pluripotent stem cell cardiomyocytes. Objective: To identify differential CAV1 versus CAV3 protein interactions and to define the molecular basis of cardiac CAV3 loss-of-function. Methods and Results: Combining stable isotope labeling with proximity proteomics, we applied mass spectrometry to screen for putative CAV3 interactors in living cardiomyocytes. Isoform-specific affinity proteomic and co-immunoprecipitation experiments confirmed the monocarboxylate transporter McT1 (monocarboxylate transporter type 1) versus aquaporin1, respectively, as CAV3 or CAV1 specific interactors in cardiomyocytes. Superresolution stimulated emission depletion microscopy showed distinct CAV1 versus CAV3 cluster distributions in cardiomyocyte transverse tubules. CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/Cas9 nuclease)-mediated CAV3 knockout uncovered a stabilizing role for McT1 surface expression, proton-coupled lactate shuttling, increased late Na + currents, and early afterdepolarizations in human induced pluripotent stem cell-derived cardiomyocytes. Complexome profiling confirmed that McT1 and the Na,K-ATPase form labile protein assemblies with the multimeric CAV3 complex. Conclusions: Combining the strengths of proximity and affinity proteomics, we identified isoform-specific CAV1 versus CAV3 binding partners in cardiomyocytes. McT1 represents a novel class of metabolically relevant CAV3-specific interactors close to mitochondria in cardiomyocyte transverse tubules. CAV3 knockout uncovered a previously unknown role for functional stabilization of McT1 in the surface membrane of human cardiomyocytes. Strikingly, CAV3 deficient cardiomyocytes exhibit action potential prolongation and instability, reproducing human reentry arrhythmias in silico. Given that lactate is a major substrate for stress adaption both in the healthy and the diseased human heart, future studies of conserved McT1/CAV3 interactions may provide rationales to target this muscle-specific assembly function therapeutically."],["dc.identifier.doi","10.1161/CIRCRESAHA.119.316547"],["dc.identifier.pmid","33486968"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85167"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/216"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/383"],["dc.identifier.url","https://sfb1190.med.uni-goettingen.de/production/literature/publications/135"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A06: Molekulare Grundlagen mitochondrialer Kardiomyopathien"],["dc.relation","SFB 1002 | A09: Lokale molekulare Nanodomänen-Regulation der kardialen Ryanodin-Rezeptor-Funktion"],["dc.relation","SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur"],["dc.relation","SFB 1002 | D02: Neue Mechanismen der genomischen Instabilität bei Herzinsuffizienz"],["dc.relation","SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle"],["dc.relation","SFB 1002 | S02: Hochauflösende Fluoreszenzmikroskopie und integrative Datenanalyse"],["dc.relation","SFB 1002 | A13: Bedeutung einer gestörten zytosolischen Calciumpufferung bei der atrialen Arrhythmogenese bei Patienten mit Herzinsuffizienz (HF)"],["dc.relation","SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente"],["dc.relation.eissn","1524-4571"],["dc.relation.issn","0009-7330"],["dc.relation.workinggroup","RG Hasenfuß"],["dc.relation.workinggroup","RG Lehnart"],["dc.relation.workinggroup","RG Rehling (Mitochondrial Protein Biogenesis)"],["dc.relation.workinggroup","RG Voigt (Molecular Pharmacology)"],["dc.relation.workinggroup","RG Brandenburg"],["dc.relation.workinggroup","RG Cyganek (Stem Cell Unit)"],["dc.relation.workinggroup","RG Lenz"],["dc.relation.workinggroup","RG Wollnik"],["dc.relation.workinggroup","RG Urlaub (Bioanalytische Massenspektrometrie)"],["dc.title","Caveolin3 Stabilizes McT1-Mediated Lactate/Proton Transport in Cardiomyocytes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]