Kohl, Tobias

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Weninger, Gunnar"],["dc.contributor.author","Pochechueva, Tatiana"],["dc.contributor.author","El Chami, Dana"],["dc.contributor.author","Luo, Xiaojing"],["dc.contributor.author","Kohl, Tobias"],["dc.contributor.author","Brandenburg, Sören"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Guan, Kaomei"],["dc.contributor.author","Lenz, Christof"],["dc.contributor.author","Lehnart, Stephan Elmar"],["dc.date.accessioned","2022-07-01T07:34:53Z"],["dc.date.available","2022-07-01T07:34:53Z"],["dc.date.issued","2022"],["dc.description.abstract","Calpains are calcium-activated neutral proteases involved in the regulation of key signaling pathways. Junctophilin-2 (JP2) is a Calpain-specific proteolytic target and essential structural protein inside Ca 2+ release units required for excitation-contraction coupling in cardiomyocytes. While downregulation of JP2 by Calpain cleavage in heart failure has been reported, the precise molecular identity of the Calpain cleavage sites and the (patho-)physiological roles of the JP2 proteolytic products remain controversial. We systematically analyzed the JP2 cleavage fragments as function of Calpain-1 versus Calpain-2 proteolytic activities, revealing that both Calpain isoforms preferentially cleave mouse JP2 at R565, but subsequently at three additional secondary Calpain cleavage sites. Moreover, we identified the Calpain-specific primary cleavage products for the first time in human iPSC-derived cardiomyocytes. Knockout of RyR2 in hiPSC-cardiomyocytes destabilized JP2 resulting in an increase of the Calpain-specific cleavage fragments. The primary N-terminal cleavage product NT 1 accumulated in the nucleus of mouse and human cardiomyocytes in a Ca 2+ -dependent manner, closely associated with euchromatic chromosomal regions, where NT 1 is proposed to function as a cardio-protective transcriptional regulator in heart failure. Taken together, our data suggest that stabilizing NT 1 by preventing secondary cleavage events by Calpain and other proteases could be an important therapeutic target for future studies."],["dc.description.sponsorship"," Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659"],["dc.description.sponsorship"," Deutsches Zentrum für Herz-Kreislaufforschung http://dx.doi.org/10.13039/100010447"],["dc.description.sponsorship","Herzzentrum Göttingen"],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.doi","10.1038/s41598-022-14320-9"],["dc.identifier.pii","14320"],["dc.identifier.pmid","35725601"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112032"],["dc.identifier.url","https://sfb1190.med.uni-goettingen.de/production/literature/publications/179"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/508"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/435"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-581"],["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","SFB 1190 | Z02: Massenspektrometrie-basierte Proteomanalyse"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A09: Lokale molekulare Nanodomänen-Regulation der kardialen Ryanodin-Rezeptor-Funktion"],["dc.relation.eissn","2045-2322"],["dc.relation.workinggroup","RG Lehnart (Cellular Biophysics and Translational Cardiology Section)"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Calpain cleavage of Junctophilin-2 generates a spectrum of calcium-dependent cleavage products and DNA-rich NT1-fragment domains in cardiomyocytes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","201"],["dc.bibliographiccitation.journal","Frontiers in physiology"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Herrmann, Solveig"],["dc.contributor.author","Ninkovic, Milena"],["dc.contributor.author","Kohl, Tobias"],["dc.contributor.author","Pardo, Luis A."],["dc.date.accessioned","2019-07-09T11:40:08Z"],["dc.date.available","2019-07-09T11:40:08Z"],["dc.date.issued","2013"],["dc.description.abstract","Although crucial for their correct function, the mechanisms controlling surface expression of ion channels are poorly understood. In the case of the voltage-gated potassium channel KV10.1, this is determinant not only for its physiological function in brain, but also for its pathophysiology in tumors and possible use as a therapeutic target. The Golgi resident protein PIST binds several membrane proteins, thereby modulating their expression. Here we describe a PDZ domain-mediated interaction of KV10.1 and PIST, which enhances surface levels of KV10.1. The functional, but not the physical interaction of both proteins is dependent on the coiled-coil and PDZ domains of PIST; insertion of eight amino acids in the coiled-coil domain to render the neural form of PIST (nPIST) and the corresponding short isoform in an as-of-yet unknown form abolishes the effect. In addition, two new isoforms of PIST (sPIST and nsPIST) lacking nearly the complete PDZ domain were cloned and shown to be ubiquitously expressed. PIST and KV10.1 co-precipitate from native and expression systems. nPIST also showed interaction, but did not alter the functional expression of the channel. We could not document physical interaction between KV10.1 and sPIST, but it reduced KV10.1 functional expression in a dominant-negative manner. nsPIST showed weak physical interaction and no functional effect on KV10.1. We propose these isoforms to work as modulators of PIST function via regulating the binding on interaction partners."],["dc.identifier.doi","10.3389/fphys.2013.00201"],["dc.identifier.fs","604131"],["dc.identifier.pmid","23966943"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10690"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58100"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1664-042X"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","PIST (GOPC) modulates the oncogenic voltage-gated potassium channel KV10.1."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e26329"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","PLOS ONE"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Kohl, Tobias"],["dc.contributor.author","Lörinczi, Eva"],["dc.contributor.author","Pardo, Luis A."],["dc.contributor.author","Stühmer, Walter"],["dc.date.accessioned","2018-11-07T08:50:44Z"],["dc.date.available","2018-11-07T08:50:44Z"],["dc.date.issued","2011"],["dc.description.abstract","K(V)10.1 is a mammalian brain voltage-gated potassium channel whose ectopic expression outside of the brain has been proven relevant for tumor biology. Promotion of cancer cell proliferation by K(V)10.1 depends largely on ion flow, but some oncogenic properties remain in the absence of ion permeation. Additionally, K(V)10.1 surface populations are small compared to large intracellular pools. Control of protein turnover within cells is key to both cellular plasticity and homeostasis, and therefore we set out to analyze how endocytic trafficking participates in controlling K(V)10.1 intracellular distribution and life cycle. To follow plasma membrane K(V)10.1 selectively, we generated a modified channel of displaying an extracellular affinity tag for surface labeling by alpha-bungarotoxin. This modification only minimally affected K(V)10.1 electrophysiological properties. Using a combination of microscopy and biochemistry techniques, we show that K(V)10.1 is constitutively internalized involving at least two distinct pathways of endocytosis and mainly sorted to lysosomes. This occurs at a relatively fast rate. Simultaneously, recycling seems to contribute to maintain basal K(V)10.1 surface levels. Brief K(V)10.1 surface half-life and rapid lysosomal targeting is a relevant factor to be taken into account for potential drug delivery and targeting strategies directed against K(V)10.1 on tumor cells."],["dc.identifier.doi","10.1371/journal.pone.0026329"],["dc.identifier.isi","000295976000098"],["dc.identifier.pmid","22022602"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8343"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21761"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","Najko"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","Rapid Internalization of the Oncogenic K+ Channel K(V)10.1"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Rudolph, Franziska"],["dc.contributor.author","Fink, Claudia"],["dc.contributor.author","Hüttemeister, Judith"],["dc.contributor.author","Kirchner, Marieluise"],["dc.contributor.author","Radke, Michael H."],["dc.contributor.author","Lopez Carballo, Jacobo"],["dc.contributor.author","Wagner, Eva"],["dc.contributor.author","Kohl, Tobias"],["dc.contributor.author","Lehnart, Stephan Elmar"],["dc.contributor.author","Mertins, Philipp"],["dc.contributor.author","Gotthardt, Michael"],["dc.date.accessioned","2021-04-14T08:25:49Z"],["dc.date.available","2021-04-14T08:25:49Z"],["dc.date.issued","2020"],["dc.description.abstract","Proximity proteomics has greatly advanced the analysis of native protein complexes and subcellular structures in culture, but has not been amenable to study development and disease in vivo. Here, we have generated a knock-in mouse with the biotin ligase (BioID) inserted at titin’s Z-disc region to identify protein networks that connect the sarcomere to signal transduction and metabolism. Our census of the sarcomeric proteome from neonatal to adult heart and quadriceps reveals how perinatal signaling, protein homeostasis and the shift to adult energy metabolism shape the properties of striated muscle cells. Mapping biotinylation sites to sarcomere structures refines our understanding of myofilament dynamics and supports the hypothesis that myosin filaments penetrate Z-discs to dampen contraction. Extending this proof of concept study to BioID fusion proteins generated with Crispr/CAS9 in animal models recapitulating human pathology will facilitate the future analysis of molecular machines and signaling hubs in physiological, pharmacological, and disease context."],["dc.identifier.doi","10.1038/s41467-020-16929-8"],["dc.identifier.pmid","32561764"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81738"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/358"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | S02: Hochauflösende Fluoreszenzmikroskopie und integrative Datenanalyse"],["dc.relation.eissn","2041-1723"],["dc.relation.workinggroup","RG Lehnart (Cellular Biophysics and Translational Cardiology Section)"],["dc.rights","CC BY 4.0"],["dc.title","Deconstructing sarcomeric structure–function relations in titin-BioID knock-in mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","13"],["dc.bibliographiccitation.journal","Journal of Molecular and Cellular Cardiology"],["dc.bibliographiccitation.lastpage","21"],["dc.bibliographiccitation.volume","58"],["dc.contributor.author","Kohl, Tobias"],["dc.contributor.author","Westphal, Volker"],["dc.contributor.author","Hell, Stefan W."],["dc.contributor.author","Lehnart, Stephan E."],["dc.date.accessioned","2017-09-07T11:47:42Z"],["dc.date.accessioned","2019-02-27T09:31:09Z"],["dc.date.available","2017-09-07T11:47:42Z"],["dc.date.available","2019-02-27T09:31:09Z"],["dc.date.issued","2013"],["dc.description.abstract","Detailed understanding of the adaptive nature of cardiac cells in health and disease requires investigation of proteins and membranes in their native physiological environment, ideally by noninvasive optical methods. However, conventional light microscopy does not resolve the spatial characteristics of small fluorescently labeled protein or membrane structures in cells. Due to diffraction limiting resolution to half the wavelength of light, adjacent fluorescent molecules spaced at less than ~250 nm are not separately visualized. This fundamental problem has lead to a rapidly growing area of research, superresolution fluorescence microscopy, also called nanoscopy. We discuss pioneering applications of superresolution microscopy relevant to the heart, emphasizing different nanoscopy strategies toward new insight in cardiac cell biology. Here, we focus on molecular and structural readouts from subcellular nanodomains and organelles related to Ca(2+) signaling during excitation-contraction (EC) coupling, including live cell imaging strategies. Based on existing data and superresolution techniques, we suggest that an important future aim will be subcellular in situ structure-function analysis with nanometric resolving power in organotypic cells."],["dc.identifier.doi","10.1016/j.yjmcc.2012.11.016"],["dc.identifier.gro","3142353"],["dc.identifier.isi","000317997600004"],["dc.identifier.pmid","23219451"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8981"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/57633"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7342"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/27"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A05: Molekulares Imaging von kardialen Calcium-Freisetzungsdomänen"],["dc.relation","SFB 1002 | A09: Lokale molekulare Nanodomänen-Regulation der kardialen Ryanodin-Rezeptor-Funktion"],["dc.relation.eissn","1095-8584"],["dc.relation.issn","0022-2828"],["dc.relation.issn","1095-8584"],["dc.relation.workinggroup","RG Hell"],["dc.relation.workinggroup","RG Lehnart (Cellular Biophysics and Translational Cardiology Section)"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Superresolution microscopy in heart - Cardiac nanoscopy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","overview_ja"],["dc.type.version","submitted_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","39464"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Rivera-Monroy, Jhon"],["dc.contributor.author","Musiol, Lena"],["dc.contributor.author","Unthan-Fechner, Kirsten"],["dc.contributor.author","Farkas, Ákos"],["dc.contributor.author","Clancy, Anne"],["dc.contributor.author","Coy-Vergara, Javier"],["dc.contributor.author","Weill, Uri"],["dc.contributor.author","Gockel, Sarah"],["dc.contributor.author","Lin, Shuh-Yow"],["dc.contributor.author","Corey, David P."],["dc.contributor.author","Kohl, Tobias"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Schuldiner, Maya"],["dc.contributor.author","Schwappach, Blanche"],["dc.contributor.author","Vilardi, Fabio"],["dc.date.accessioned","2018-04-23T11:49:05Z"],["dc.date.available","2018-04-23T11:49:05Z"],["dc.date.issued","2016"],["dc.description.abstract","Tail-anchored (TA) proteins are post-translationally inserted into membranes. The TRC40 pathway targets TA proteins to the endoplasmic reticulum via a receptor comprised of WRB and CAML. TRC40 pathway clients have been identified using in vitro assays, however, the relevance of the TRC40 pathway in vivo remains unknown. We followed the fate of TA proteins in two tissue-specific WRB knockout mouse models and found that their dependence on the TRC40 pathway in vitro did not predict their reaction to receptor depletion in vivo. The SNARE syntaxin 5 (Stx5) was extremely sensitive to disruption of the TRC40 pathway. Screening yeast TA proteins with mammalian homologues, we show that the particular sensitivity of Stx5 is conserved, possibly due to aggregation propensity of its cytoplasmic domain. We establish that Stx5 is an autophagy target that is inefficiently membrane-targeted by alternative pathways. Our results highlight an intimate relationship between the TRC40 pathway and cellular proteostasis."],["dc.identifier.doi","10.1038/srep39464"],["dc.identifier.gro","3142486"],["dc.identifier.pmid","28000760"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14116"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13638"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/187"],["dc.identifier.url","https://sfb1190.med.uni-goettingen.de/production/literature/publications/8"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A06: Molekulare Grundlagen mitochondrialer Kardiomyopathien"],["dc.relation","SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente"],["dc.relation","SFB 1190 | P04: Der GET-Rezeptor als ein Eingangstor zum ER und sein Zusammenspiel mit GET bodies"],["dc.relation","SFB 1190 | P11: Zuordnung zellulärer Kontaktstellen und deren Zusammenspiel"],["dc.relation.issn","2045-2322"],["dc.relation.workinggroup","RG Lehnart (Cellular Biophysics and Translational Cardiology Section)"],["dc.relation.workinggroup","RG Schwappach (Membrane Protein Biogenesis)"],["dc.relation.workinggroup","RG Schuldiner (Functional Genomics of Organelles)"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Mice lacking WRB reveal differential biogenesis requirements of tail-anchored proteins in vivo"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","1227"],["dc.bibliographiccitation.journal","Frontiers in Physiology"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Brandenburg, Sören"],["dc.contributor.author","Pawlowitz, Jan"],["dc.contributor.author","Lehnart, Stephan Elmar"],["dc.contributor.author","Fakuade, Funsho E."],["dc.contributor.author","Kownatzki-Danger, Daniel"],["dc.contributor.author","Kohl, Tobias"],["dc.contributor.author","Mitronova, Gyuzel Y."],["dc.contributor.author","Scardigli, Marina"],["dc.contributor.author","Neef, Jakob"],["dc.contributor.author","Schmidt, Constanze"],["dc.contributor.author","Wiedmann, Felix"],["dc.contributor.author","Pavone, Francesco S."],["dc.contributor.author","Sacconi, Leonardo"],["dc.contributor.author","Kutschka, Ingo"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Voigt, Niels"],["dc.date.accessioned","2022-05-13T09:20:22Z"],["dc.date.available","2022-05-13T09:20:22Z"],["dc.date.issued","2018-07-13"],["dc.description.abstract","Rationale: Recently, abundant axial tubule (AT) membrane structures were identified deep inside atrial myocytes (AMs). Upon excitation, ATs rapidly activate intracellular Ca2+ release and sarcomeric contraction through extensive AT junctions, a cell-specific atrial mechanism. While AT junctions with the sarcoplasmic reticulum contain unusually large clusters of ryanodine receptor 2 (RyR2) Ca2+ release channels in mouse AMs, it remains unclear if similar protein networks and membrane structures exist across species, particularly those relevant for atrial disease modeling. Objective: To examine and quantitatively analyze the architecture of AT membrane structures and associated Ca2+ signaling proteins across species from mouse to human. Methods and Results: We developed superresolution microscopy (nanoscopy) strategies for intact live AMs based on a new custom-made photostable cholesterol dye and immunofluorescence imaging of membraneous structures and membrane proteins in fixed tissue sections from human, porcine, and rodent atria. Consistently, in mouse, rat, and rabbit AMs, intact cell-wide tubule networks continuous with the surface membrane were observed, mainly composed of ATs. Moreover, co-immunofluorescence nanoscopy showed L-type Ca2+ channel clusters adjacent to extensive junctional RyR2 clusters at ATs. However, only junctional RyR2 clusters were highly phosphorylated and may thus prime Ca2+ release at ATs, locally for rapid signal amplification. While the density of the integrated L-type Ca2+ current was similar in human and mouse AMs, the intracellular Ca2+ transient showed quantitative differences. Importantly, local intracellular Ca2+ release from AT junctions occurred through instantaneous action potential propagation via transverse tubules (TTs) from the surface membrane. Hence, sparse TTs were sufficient as electrical conduits for rapid activation of Ca2+ release through ATs. Nanoscopy of atrial tissue sections confirmed abundant ATs as the major network component of AMs, particularly in human atrial tissue sections. Conclusion: AT junctions represent a conserved, cell-specific membrane structure for rapid excitation-contraction coupling throughout a representative spectrum of species including human. Since ATs provide the major excitable membrane network component in AMs, a new model of atrial \"super-hub\" Ca2+ signaling may apply across biomedically relevant species, opening avenues for future investigations about atrial disease mechanisms and therapeutic targeting."],["dc.identifier.doi","10.3389/fphys.2018.01227"],["dc.identifier.pmid","30349482"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15400"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/107860"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/217"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A05: Molekulares Imaging von kardialen Calcium-Freisetzungsdomänen"],["dc.relation","SFB 1002 | A09: Lokale molekulare Nanodomänen-Regulation der kardialen Ryanodin-Rezeptor-Funktion"],["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.eissn","1664-042X"],["dc.relation.workinggroup","RG Brandenburg"],["dc.relation.workinggroup","RG Lehnart (Cellular Biophysics and Translational Cardiology Section)"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.relation.workinggroup","RG Voigt (Molecular Pharmacology)"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Axial Tubule Junctions Activate Atrial Ca2+ Release across Species"],["dc.type","research_data"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3018"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Biophysical Journal"],["dc.bibliographiccitation.lastpage","3029"],["dc.bibliographiccitation.volume","107"],["dc.contributor.author","Walker, Mark A."],["dc.contributor.author","Williams, George S. B."],["dc.contributor.author","Kohl, Tobias"],["dc.contributor.author","Lehnart, Stephan Elmar"],["dc.contributor.author","Jafri, M. Saleet"],["dc.contributor.author","Greenstein, Joseph L."],["dc.contributor.author","Lederer, W. J."],["dc.contributor.author","Winslow, Raimond L."],["dc.date.accessioned","2018-05-07T13:09:57Z"],["dc.date.available","2018-05-07T13:09:57Z"],["dc.date.issued","2014"],["dc.description.abstract","Stable calcium-induced calcium release (CICR) is critical for maintaining normal cellular contraction during cardiac excitation-contraction coupling. The fundamental element of CICR in the heart is the calcium (Ca(2+)) spark, which arises from a cluster of ryanodine receptors (RyR). Opening of these RyR clusters is triggered to produce a local, regenerative release of Ca(2+) from the sarcoplasmic reticulum (SR). The Ca(2+) leak out of the SR is an important process for cellular Ca(2+) management, and it is critically influenced by spark fidelity, i.e., the probability that a spontaneous RyR opening triggers a Ca(2+) spark. Here, we present a detailed, three-dimensional model of a cardiac Ca(2+) release unit that incorporates diffusion, intracellular buffering systems, and stochastically gated ion channels. The model exhibits realistic Ca(2+) sparks and robust Ca(2+) spark termination across a wide range of geometries and conditions. Furthermore, the model captures the details of Ca(2+) spark and nonspark-based SR Ca(2+) leak, and it produces normal excitation-contraction coupling gain. We show that SR luminal Ca(2+)-dependent regulation of the RyR is not critical for spark termination, but it can explain the exponential rise in the SR Ca(2+) leak-load relationship demonstrated in previous experimental work. Perturbations to subspace dimensions, which have been observed in experimental models of disease, strongly alter Ca(2+) spark dynamics. In addition, we find that the structure of RyR clusters also influences Ca(2+) release properties due to variations in inter-RyR coupling via local subspace Ca(2+) concentration ([Ca(2+)]ss). These results are illustrated for RyR clusters based on super-resolution stimulated emission depletion microscopy. Finally, we present a believed-novel approach by which the spark fidelity of a RyR cluster can be predicted from structural information of the cluster using the maximum eigenvalue of its adjacency matrix. These results provide critical insights into CICR dynamics in heart, under normal and pathological conditions."],["dc.identifier.doi","10.1016/j.bpj.2014.11.003"],["dc.identifier.pmid","25517166"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11349"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/14631"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.doi","10.1016/j.bpj.2014.11.003"],["dc.relation.eissn","1542-0086"],["dc.relation.issn","1542-0086"],["dc.rights","CC BY-NC-ND 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/3.0"],["dc.title","Superresolution modeling of calcium release in the heart"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e8858"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Gómez-Varela, David"],["dc.contributor.author","Kohl, Tobias"],["dc.contributor.author","Schmidt, Manuela"],["dc.contributor.author","Rubio, María E."],["dc.contributor.author","Kawabe, Hiroshi"],["dc.contributor.author","Nehring, Ralf B."],["dc.contributor.author","Schäfer, Stephan"],["dc.contributor.author","Stühmer, Walter"],["dc.contributor.author","Pardo, Luis A."],["dc.date.accessioned","2019-07-09T11:54:01Z"],["dc.date.available","2019-07-09T11:54:01Z"],["dc.date.issued","2010-01-25"],["dc.description.abstract","Voltage-gated ion channels are main players involved in fast synaptic events. However, only slow intracellular mechanisms have so far been described for controlling their localization as real-time visualization of endogenous voltage-gated channels at high temporal and spatial resolution has not been achieved yet. Using a specific extracellular antibody and quantum dots we reveal and characterize lateral mobility as a faster mechanism to dynamically control the number of endogenous ethera- go-go (Eag)1 ion channels inside synapses. We visualize Eag1 entering and leaving synapses by lateral diffusion in the plasma membrane of rat hippocampal neurons. Mathematical analysis of their trajectories revealed how the motion of Eag1 gets restricted when the channels diffuse into the synapse, suggesting molecular interactions between Eag1 and synaptic components. In contrast, Eag1 channels switch to Brownian movement when they exit synapses and diffuse into extrasynaptic membranes. Furthermore, we demonstrate that the mobility of Eag1 channels is specifically regulated inside synapses by actin filaments, microtubules and electrical activity. In summary, using single-particle-tracking techniques with quantum dots nanocrystals, our study shows for the first time the lateral diffusion of an endogenous voltage-gated ion channel in neurons. The location-dependent constraints imposed by cytoskeletal elements together with the regulatory role of electrical activity strongly suggest a pivotal role for the mobility of voltage-gated ion channels in synaptic activity."],["dc.format.extent","9"],["dc.identifier.doi","10.1371/journal.pone.0008858"],["dc.identifier.pmid","20111597"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8309"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60549"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","Characterization of Eag1 Channel Lateral Mobility in Rat Hippocampal Cultures by Single-Particle-Tracking with Quantum Dots"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","141"],["dc.bibliographiccitation.journal","Journal of Molecular and Cellular Cardiology"],["dc.bibliographiccitation.lastpage","157"],["dc.bibliographiccitation.volume","165"],["dc.contributor.author","Brandenburg, Sören"],["dc.contributor.author","Pawlowitz, Jan"],["dc.contributor.author","Steckmeister, Vanessa"],["dc.contributor.author","Subramanian, Hariharan"],["dc.contributor.author","Uhlenkamp, Dennis"],["dc.contributor.author","Scardigli, Marina"],["dc.contributor.author","Mushtaq, Mufassra"],["dc.contributor.author","Amlaz, Saskia I."],["dc.contributor.author","Kohl, Tobias"],["dc.contributor.author","Wegener, Jörg W."],["dc.contributor.author","Lehnart, Stephan E."],["dc.date.accessioned","2022-02-01T10:32:12Z"],["dc.date.available","2022-02-01T10:32:12Z"],["dc.date.issued","2022"],["dc.description.abstract","Axial tubule junctions with the sarcoplasmic reticulum control the rapid intracellular Ca2+-induced Ca2+ release that initiates atrial contraction. In atrial myocytes we previously identified a constitutively increased ryanodine receptor (RyR2) phosphorylation at junctional Ca2+ release sites, whereas non-junctional RyR2 clusters were phosphorylated acutely following β-adrenergic stimulation. Here, we hypothesized that the baseline synthesis of 3′,5′-cyclic adenosine monophosphate (cAMP) is constitutively augmented in the axial tubule junctional compartments of atrial myocytes. Confocal immunofluorescence imaging of atrial myocytes revealed that junctin, binding to RyR2 in the sarcoplasmic reticulum, was densely clustered at axial tubule junctions. Interestingly, a new transgenic junctin-targeted FRET cAMP biosensor was exclusively co-clustered in the junctional compartment, and hence allowed to monitor cAMP selectively in the vicinity of junctional RyR2 channels. To dissect local cAMP levels at axial tubule junctions versus subsurface Ca2+ release sites, we developed a confocal FRET imaging technique for living atrial myocytes. A constitutively high adenylyl cyclase activity sustained increased local cAMP levels at axial tubule junctions, whereas β-adrenergic stimulation overcame this cAMP compartmentation resulting in additional phosphorylation of non-junctional RyR2 clusters. Adenylyl cyclase inhibition, however, abolished the junctional RyR2 phosphorylation and decreased L-type Ca2+ channel currents, while FRET imaging showed a rapid cAMP decrease. In conclusion, FRET biosensor imaging identified compartmentalized, constitutively augmented cAMP levels in junctional dyads, driving both the locally increased phosphorylation of RyR2 clusters and larger L-type Ca2+ current density in atrial myocytes. This cell-specific cAMP nanodomain is maintained by a constitutively increased adenylyl cyclase activity, contributing to the rapid junctional Ca2+-induced Ca2+ release, whereas β-adrenergic stimulation overcomes the junctional cAMP compartmentation through cell-wide activation of non-junctional RyR2 clusters."],["dc.identifier.doi","10.1016/j.yjmcc.2022.01.003"],["dc.identifier.pii","S0022282822000062"],["dc.identifier.pmid","35033544"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/99034"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/391"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/414"],["dc.identifier.url","https://sfb1190.med.uni-goettingen.de/production/literature/publications/168"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-517"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["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.issn","0022-2828"],["dc.relation.workinggroup","RG Hasenfuß"],["dc.relation.workinggroup","RG Lehnart"],["dc.relation.workinggroup","RG Voigt (Molecular Pharmacology)"],["dc.relation.workinggroup","RG Brandenburg"],["dc.relation.workinggroup","RG Nikolaev (Cardiovascular Research Center)"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://www.elsevier.com/tdm/userlicense/1.0/"],["dc.title","A junctional cAMP compartment regulates rapid Ca2+ signaling in atrial myocytes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]