Dysferlin Enables Tubular Membrane Proliferation in Cardiac Hypertrophy.

cell membrane constriction dysferin mice phenotype

Journal

Circulation research
ISSN: 1524-4571
Titre abrégé: Circ Res
Pays: United States
ID NLM: 0047103

Informations de publication

Date de publication:
16 Jul 2024
Historique:
medline: 16 7 2024
pubmed: 16 7 2024
entrez: 16 7 2024
Statut: aheadofprint

Résumé

Cardiac hypertrophy compensates for increased biomechanical stress of the heart induced by prevalent cardiovascular pathologies but can result in cardiac failure if left untreated. We hypothesized that the tail-anchored protein dysferlin with multiple Ca To reveal the impact of the membrane fusion and repair protein dysferlin on TAT network stabilization and proliferation necessary for the hypertrophic growth of cardiomyocytes. Super-resolution light and electron microscopy of mouse cardiomyocytes identified a specific localization of dysferlin in a vesicular compartment in nanometric proximity to contact sites of the TAT network with the sarcoplasmic reticulum, a.k.a. junctional complexes for Ca Dysferlin represents a new molecular target in cardiac disease that protects the integrity of tubule-sarcoplasmic reticulum junctional complexes for regulated excitation-contraction coupling and controls TAT network reorganization and tubular membrane proliferation in cardiomyocyte hypertrophy induced by pressure overload.

Sections du résumé

BACKGROUND UNASSIGNED
Cardiac hypertrophy compensates for increased biomechanical stress of the heart induced by prevalent cardiovascular pathologies but can result in cardiac failure if left untreated. We hypothesized that the tail-anchored protein dysferlin with multiple Ca
OBJECTIVE UNASSIGNED
To reveal the impact of the membrane fusion and repair protein dysferlin on TAT network stabilization and proliferation necessary for the hypertrophic growth of cardiomyocytes.
METHODS AND RESULTS UNASSIGNED
Super-resolution light and electron microscopy of mouse cardiomyocytes identified a specific localization of dysferlin in a vesicular compartment in nanometric proximity to contact sites of the TAT network with the sarcoplasmic reticulum, a.k.a. junctional complexes for Ca
CONCLUSIONS UNASSIGNED
Dysferlin represents a new molecular target in cardiac disease that protects the integrity of tubule-sarcoplasmic reticulum junctional complexes for regulated excitation-contraction coupling and controls TAT network reorganization and tubular membrane proliferation in cardiomyocyte hypertrophy induced by pressure overload.

Identifiants

DOI: 10.1161/CIRCRESAHA.124.324588 PMID: 39011635
pubmed: 39011635
doi: 10.1161/CIRCRESAHA.124.324588
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Auteurs

Nora Josefine Paulke (NJ)

Department of Cardiology and Pneumology, University Medical Center Göttingen, Germany. (N.J.P., C.F., J.B.W., G.C.R., M.M., N.Z., Y.Z., J.W., L.L., A.A.G., D.K.-D., E.W., T.K., K.T., G.H., S.E.L., S.B.).
Cellular Biophysics and Translational Cardiology Section, Heart Research Center, University Medical Center Göttingen, Germany. (N.J.P., C.F., J.B.W., G.C.R., M.M., N.Z., Y.Z., J.W., L.L., A.A.G., D.K.-D., E.W., T.K., S.E.L., S.B.).
ORCID: 0000-0002-0027-7937

Carolin Fleischhacker (C)

Department of Cardiology and Pneumology, University Medical Center Göttingen, Germany. (N.J.P., C.F., J.B.W., G.C.R., M.M., N.Z., Y.Z., J.W., L.L., A.A.G., D.K.-D., E.W., T.K., K.T., G.H., S.E.L., S.B.).
Cellular Biophysics and Translational Cardiology Section, Heart Research Center, University Medical Center Göttingen, Germany. (N.J.P., C.F., J.B.W., G.C.R., M.M., N.Z., Y.Z., J.W., L.L., A.A.G., D.K.-D., E.W., T.K., S.E.L., S.B.).

Justus B Wegener (JB)

Department of Cardiology and Pneumology, University Medical Center Göttingen, Germany. (N.J.P., C.F., J.B.W., G.C.R., M.M., N.Z., Y.Z., J.W., L.L., A.A.G., D.K.-D., E.W., T.K., K.T., G.H., S.E.L., S.B.).
Cellular Biophysics and Translational Cardiology Section, Heart Research Center, University Medical Center Göttingen, Germany. (N.J.P., C.F., J.B.W., G.C.R., M.M., N.Z., Y.Z., J.W., L.L., A.A.G., D.K.-D., E.W., T.K., S.E.L., S.B.).
ORCID: 0009-0001-0714-7019

Gabriel C Riedemann (GC)

Department of Cardiology and Pneumology, University Medical Center Göttingen, Germany. (N.J.P., C.F., J.B.W., G.C.R., M.M., N.Z., Y.Z., J.W., L.L., A.A.G., D.K.-D., E.W., T.K., K.T., G.H., S.E.L., S.B.).
Cellular Biophysics and Translational Cardiology Section, Heart Research Center, University Medical Center Göttingen, Germany. (N.J.P., C.F., J.B.W., G.C.R., M.M., N.Z., Y.Z., J.W., L.L., A.A.G., D.K.-D., E.W., T.K., S.E.L., S.B.).

Constantin Cretu (C)

Biochemistry of Membrane Dynamics Group, Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Germany. (C.C., J.P.).
ORCID: 0000-0002-6466-176X

Mufassra Mushtaq (M)

Department of Cardiology and Pneumology, University Medical Center Göttingen, Germany. (N.J.P., C.F., J.B.W., G.C.R., M.M., N.Z., Y.Z., J.W., L.L., A.A.G., D.K.-D., E.W., T.K., K.T., G.H., S.E.L., S.B.).
Cellular Biophysics and Translational Cardiology Section, Heart Research Center, University Medical Center Göttingen, Germany. (N.J.P., C.F., J.B.W., G.C.R., M.M., N.Z., Y.Z., J.W., L.L., A.A.G., D.K.-D., E.W., T.K., S.E.L., S.B.).
Cluster of Excellence "Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells" (MBExC), University of Göttingen, Germany (W.M., C.W., H.U., K.T., G.H., T.M., J.P., C.L., S.E.L., S.B.).
ORCID: 0000-0002-7510-6868

Nina Zaremba (N)

Department of Cardiology and Pneumology, University Medical Center Göttingen, Germany. (N.J.P., C.F., J.B.W., G.C.R., M.M., N.Z., Y.Z., J.W., L.L., A.A.G., D.K.-D., E.W., T.K., K.T., G.H., S.E.L., S.B.).
Cellular Biophysics and Translational Cardiology Section, Heart Research Center, University Medical Center Göttingen, Germany. (N.J.P., C.F., J.B.W., G.C.R., M.M., N.Z., Y.Z., J.W., L.L., A.A.G., D.K.-D., E.W., T.K., S.E.L., S.B.).

Wiebke Möbius (W)

Department of Neurogenetics, Electron Microscopy, City Campus (W.M.).
ORCID: 0000-0002-2902-7165

Yannik Zühlke (Y)

Department of Cardiology and Pneumology, University Medical Center Göttingen, Germany. (N.J.P., C.F., J.B.W., G.C.R., M.M., N.Z., Y.Z., J.W., L.L., A.A.G., D.K.-D., E.W., T.K., K.T., G.H., S.E.L., S.B.).
Cellular Biophysics and Translational Cardiology Section, Heart Research Center, University Medical Center Göttingen, Germany. (N.J.P., C.F., J.B.W., G.C.R., M.M., N.Z., Y.Z., J.W., L.L., A.A.G., D.K.-D., E.W., T.K., S.E.L., S.B.).
ORCID: 0009-0002-6543-438X

Jasper Wedemeyer (J)

Department of Cardiology and Pneumology, University Medical Center Göttingen, Germany. (N.J.P., C.F., J.B.W., G.C.R., M.M., N.Z., Y.Z., J.W., L.L., A.A.G., D.K.-D., E.W., T.K., K.T., G.H., S.E.L., S.B.).
Cellular Biophysics and Translational Cardiology Section, Heart Research Center, University Medical Center Göttingen, Germany. (N.J.P., C.F., J.B.W., G.C.R., M.M., N.Z., Y.Z., J.W., L.L., A.A.G., D.K.-D., E.W., T.K., S.E.L., S.B.).

Lorenz Liebmann (L)

Department of Cardiology and Pneumology, University Medical Center Göttingen, Germany. (N.J.P., C.F., J.B.W., G.C.R., M.M., N.Z., Y.Z., J.W., L.L., A.A.G., D.K.-D., E.W., T.K., K.T., G.H., S.E.L., S.B.).
Cellular Biophysics and Translational Cardiology Section, Heart Research Center, University Medical Center Göttingen, Germany. (N.J.P., C.F., J.B.W., G.C.R., M.M., N.Z., Y.Z., J.W., L.L., A.A.G., D.K.-D., E.W., T.K., S.E.L., S.B.).

Anastasiia A Gorshkova (AA)

Department of Cardiology and Pneumology, University Medical Center Göttingen, Germany. (N.J.P., C.F., J.B.W., G.C.R., M.M., N.Z., Y.Z., J.W., L.L., A.A.G., D.K.-D., E.W., T.K., K.T., G.H., S.E.L., S.B.).
Cellular Biophysics and Translational Cardiology Section, Heart Research Center, University Medical Center Göttingen, Germany. (N.J.P., C.F., J.B.W., G.C.R., M.M., N.Z., Y.Z., J.W., L.L., A.A.G., D.K.-D., E.W., T.K., S.E.L., S.B.).

Daniel Kownatzki-Danger (D)

Department of Cardiology and Pneumology, University Medical Center Göttingen, Germany. (N.J.P., C.F., J.B.W., G.C.R., M.M., N.Z., Y.Z., J.W., L.L., A.A.G., D.K.-D., E.W., T.K., K.T., G.H., S.E.L., S.B.).
Cellular Biophysics and Translational Cardiology Section, Heart Research Center, University Medical Center Göttingen, Germany. (N.J.P., C.F., J.B.W., G.C.R., M.M., N.Z., Y.Z., J.W., L.L., A.A.G., D.K.-D., E.W., T.K., S.E.L., S.B.).
Now with Institute of Transfusion Medicine, University Hospital Schleswig-Holstein; Kiel, Germany (D.K.-D).

Eva Wagner (E)

Department of Cardiology and Pneumology, University Medical Center Göttingen, Germany. (N.J.P., C.F., J.B.W., G.C.R., M.M., N.Z., Y.Z., J.W., L.L., A.A.G., D.K.-D., E.W., T.K., K.T., G.H., S.E.L., S.B.).
Cellular Biophysics and Translational Cardiology Section, Heart Research Center, University Medical Center Göttingen, Germany. (N.J.P., C.F., J.B.W., G.C.R., M.M., N.Z., Y.Z., J.W., L.L., A.A.G., D.K.-D., E.W., T.K., S.E.L., S.B.).
ORCID: 0000-0003-3128-1397

Tobias Kohl (T)

Department of Cardiology and Pneumology, University Medical Center Göttingen, Germany. (N.J.P., C.F., J.B.W., G.C.R., M.M., N.Z., Y.Z., J.W., L.L., A.A.G., D.K.-D., E.W., T.K., K.T., G.H., S.E.L., S.B.).
Cellular Biophysics and Translational Cardiology Section, Heart Research Center, University Medical Center Göttingen, Germany. (N.J.P., C.F., J.B.W., G.C.R., M.M., N.Z., Y.Z., J.W., L.L., A.A.G., D.K.-D., E.W., T.K., S.E.L., S.B.).
ORCID: 0000-0002-4407-3530

Carolin Wichmann (C)

Molecular Architecture of Synapses Group, Institute for Auditory Neuroscience and InnerEarLab and Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Germany. (C.W.).
Cluster of Excellence "Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells" (MBExC), University of Göttingen, Germany (W.M., C.W., H.U., K.T., G.H., T.M., J.P., C.L., S.E.L., S.B.).
ORCID: 0000-0001-8868-8716

Olaf Jahn (O)

Translational Neuroproteomics Group, Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Germany. (O.J.).
Neuroproteomics Group, Department of Molecular Neurobiology (O.J.).
ORCID: 0000-0002-3397-8924

Henning Urlaub (H)

Department of Clinical Chemistry, University Medical Center Göttingen, Germany. (H.U., C.L.).
Bioanalytical Mass Spectrometry Group, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany (H.U., C.L.).
Cluster of Excellence "Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells" (MBExC), University of Göttingen, Germany (W.M., C.W., H.U., K.T., G.H., T.M., J.P., C.L., S.E.L., S.B.).

Karl Toischer (K)

Cluster of Excellence "Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells" (MBExC), University of Göttingen, Germany (W.M., C.W., H.U., K.T., G.H., T.M., J.P., C.L., S.E.L., S.B.).
DZHK (German Centre for Cardiovascular Research), Partner Site Göttingen, Germany (K.T., G.H., S.E.L.).
ORCID: 0000-0002-9644-3716

Gerd Hasenfuß (G)

Cluster of Excellence "Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells" (MBExC), University of Göttingen, Germany (W.M., C.W., H.U., K.T., G.H., T.M., J.P., C.L., S.E.L., S.B.).
DZHK (German Centre for Cardiovascular Research), Partner Site Göttingen, Germany (K.T., G.H., S.E.L.).

Tobias Moser (T)

Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Germany. (T.M.).
Cluster of Excellence "Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells" (MBExC), University of Göttingen, Germany (W.M., C.W., H.U., K.T., G.H., T.M., J.P., C.L., S.E.L., S.B.).
ORCID: 0000-0001-7145-0533

Julia Preobraschenski (J)

Biochemistry of Membrane Dynamics Group, Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Germany. (C.C., J.P.).
Cluster of Excellence "Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells" (MBExC), University of Göttingen, Germany (W.M., C.W., H.U., K.T., G.H., T.M., J.P., C.L., S.E.L., S.B.).

Christof Lenz (C)

Department of Clinical Chemistry, University Medical Center Göttingen, Germany. (H.U., C.L.).
Bioanalytical Mass Spectrometry Group, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany (H.U., C.L.).
Cluster of Excellence "Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells" (MBExC), University of Göttingen, Germany (W.M., C.W., H.U., K.T., G.H., T.M., J.P., C.L., S.E.L., S.B.).
ORCID: 0000-0002-0946-8166

Eva A Rog-Zielinska (EA)

Institute for Experimental Cardiovascular Medicine, University Heart Center and Faculty of Medicine, University of Freiburg, Germany (E.A.R.-Z.).
ORCID: 0000-0002-3295-4728

Stephan E Lehnart (SE)

Department of Cardiology and Pneumology, University Medical Center Göttingen, Germany. (N.J.P., C.F., J.B.W., G.C.R., M.M., N.Z., Y.Z., J.W., L.L., A.A.G., D.K.-D., E.W., T.K., K.T., G.H., S.E.L., S.B.).
Cellular Biophysics and Translational Cardiology Section, Heart Research Center, University Medical Center Göttingen, Germany. (N.J.P., C.F., J.B.W., G.C.R., M.M., N.Z., Y.Z., J.W., L.L., A.A.G., D.K.-D., E.W., T.K., S.E.L., S.B.).
Cluster of Excellence "Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells" (MBExC), University of Göttingen, Germany (W.M., C.W., H.U., K.T., G.H., T.M., J.P., C.L., S.E.L., S.B.).
DZHK (German Centre for Cardiovascular Research), Partner Site Göttingen, Germany (K.T., G.H., S.E.L.).
ORCID: 0000-0002-8115-3513

Sören Brandenburg (S)

Department of Cardiology and Pneumology, University Medical Center Göttingen, Germany. (N.J.P., C.F., J.B.W., G.C.R., M.M., N.Z., Y.Z., J.W., L.L., A.A.G., D.K.-D., E.W., T.K., K.T., G.H., S.E.L., S.B.).
Cellular Biophysics and Translational Cardiology Section, Heart Research Center, University Medical Center Göttingen, Germany. (N.J.P., C.F., J.B.W., G.C.R., M.M., N.Z., Y.Z., J.W., L.L., A.A.G., D.K.-D., E.W., T.K., S.E.L., S.B.).
Cluster of Excellence "Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells" (MBExC), University of Göttingen, Germany (W.M., C.W., H.U., K.T., G.H., T.M., J.P., C.L., S.E.L., S.B.).
ORCID: 0000-0001-5148-0997

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