BIN1, Myotubularin, and Dynamin-2 Coordinate T-Tubule Growth in Cardiomyocytes.


Journal

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

Informations de publication

Date de publication:
26 05 2023
Historique:
medline: 29 5 2023
pubmed: 4 5 2023
entrez: 4 5 2023
Statut: ppublish

Résumé

Transverse tubules (t-tubules) form gradually in the developing heart, critically enabling maturation of cardiomyocyte Ca We investigated the roles of BIN1, MTM1, and DNM2 in t-tubule formation in developing mouse cardiomyocytes, and in gene-modified HL-1 and human-induced pluripotent stem cell-derived cardiomyocytes. T-tubules and proteins of interest were imaged by confocal and Airyscan microscopy, and expression patterns were examined by RT-qPCR and Western blotting. Ca We observed that in the postnatal mouse heart, BIN1 localizes along Z-lines from early developmental stages, consistent with roles in initial budding and scaffolding of t-tubules. T-tubule proliferation and organization were linked to a progressive and parallel increase in 4 detected BIN1 isoforms. All isoforms were observed to induce tubulation in cardiomyocytes but produced t-tubules with differing geometries. BIN1-induced tubulations contained the L-type Ca These findings indicate that BIN1, MTM1, and DNM2 have balanced and collaborative roles in controlling t-tubule growth in cardiomyocytes.

Sections du résumé

BACKGROUND
Transverse tubules (t-tubules) form gradually in the developing heart, critically enabling maturation of cardiomyocyte Ca
METHODS
We investigated the roles of BIN1, MTM1, and DNM2 in t-tubule formation in developing mouse cardiomyocytes, and in gene-modified HL-1 and human-induced pluripotent stem cell-derived cardiomyocytes. T-tubules and proteins of interest were imaged by confocal and Airyscan microscopy, and expression patterns were examined by RT-qPCR and Western blotting. Ca
RESULTS
We observed that in the postnatal mouse heart, BIN1 localizes along Z-lines from early developmental stages, consistent with roles in initial budding and scaffolding of t-tubules. T-tubule proliferation and organization were linked to a progressive and parallel increase in 4 detected BIN1 isoforms. All isoforms were observed to induce tubulation in cardiomyocytes but produced t-tubules with differing geometries. BIN1-induced tubulations contained the L-type Ca
CONCLUSIONS
These findings indicate that BIN1, MTM1, and DNM2 have balanced and collaborative roles in controlling t-tubule growth in cardiomyocytes.

Identifiants

pubmed: 37139790
doi: 10.1161/CIRCRESAHA.122.321732
doi:

Substances chimiques

Adaptor Proteins, Signal Transducing 0
BIN1 protein, human 0
Bin1 protein, mouse 0
Dynamin II EC 3.6.5.5
myotubularin EC 3.1.3.48
Nerve Tissue Proteins 0
Nuclear Proteins 0
Protein Isoforms 0
Protein Tyrosine Phosphatases, Non-Receptor EC 3.1.3.48
Tumor Suppressor Proteins 0
DNM2 protein, human EC 3.6.5.5
DNM2 protein, mouse EC 3.6.5.5

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e188-e205

Auteurs

Harmonie Perdreau-Dahl (H)

Institute for Experimental Medical Research (IEMR), Oslo University Hospital and University of Oslo, Norway (H.P.-D., D.B.L., M.F., C.R.C., X.S., A.B.-D., Y.H., M.L., G.C., J.P.M., W.E.L.).
KG Jebsen Center for Cardiac Research, University of Oslo, Norway (H.P.-D., D.B.L., M.F., X.S., A.B.-D., Y.H., M.L., G.C., W.E.L.).
Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership University of Oslo, Norway (H.P.-D., J.P.M.).
Institut MitoVasc, CNRS UMR 6015, INSERM U1083, Université d'Angers, France (H.P.-D.).

David B Lipsett (DB)

Institute for Experimental Medical Research (IEMR), Oslo University Hospital and University of Oslo, Norway (H.P.-D., D.B.L., M.F., C.R.C., X.S., A.B.-D., Y.H., M.L., G.C., J.P.M., W.E.L.).
KG Jebsen Center for Cardiac Research, University of Oslo, Norway (H.P.-D., D.B.L., M.F., X.S., A.B.-D., Y.H., M.L., G.C., W.E.L.).

Michael Frisk (M)

Institute for Experimental Medical Research (IEMR), Oslo University Hospital and University of Oslo, Norway (H.P.-D., D.B.L., M.F., C.R.C., X.S., A.B.-D., Y.H., M.L., G.C., J.P.M., W.E.L.).
KG Jebsen Center for Cardiac Research, University of Oslo, Norway (H.P.-D., D.B.L., M.F., X.S., A.B.-D., Y.H., M.L., G.C., W.E.L.).

Fatemeh Kermani (F)

Division of Cardiovascular Physiology, Institute of Physiology and Pathophysiology, Heidelberg University, Germany (F.K., N.D.U.).

Cathrine R Carlson (CR)

Institute for Experimental Medical Research (IEMR), Oslo University Hospital and University of Oslo, Norway (H.P.-D., D.B.L., M.F., C.R.C., X.S., A.B.-D., Y.H., M.L., G.C., J.P.M., W.E.L.).

Andreas Brech (A)

Department of Molecular Cell Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, Norway (A.B.).

Xin Shen (X)

Institute for Experimental Medical Research (IEMR), Oslo University Hospital and University of Oslo, Norway (H.P.-D., D.B.L., M.F., C.R.C., X.S., A.B.-D., Y.H., M.L., G.C., J.P.M., W.E.L.).
KG Jebsen Center for Cardiac Research, University of Oslo, Norway (H.P.-D., D.B.L., M.F., X.S., A.B.-D., Y.H., M.L., G.C., W.E.L.).

Anna Bergan-Dahl (A)

Institute for Experimental Medical Research (IEMR), Oslo University Hospital and University of Oslo, Norway (H.P.-D., D.B.L., M.F., C.R.C., X.S., A.B.-D., Y.H., M.L., G.C., J.P.M., W.E.L.).
KG Jebsen Center for Cardiac Research, University of Oslo, Norway (H.P.-D., D.B.L., M.F., X.S., A.B.-D., Y.H., M.L., G.C., W.E.L.).

Yufeng Hou (Y)

Institute for Experimental Medical Research (IEMR), Oslo University Hospital and University of Oslo, Norway (H.P.-D., D.B.L., M.F., C.R.C., X.S., A.B.-D., Y.H., M.L., G.C., J.P.M., W.E.L.).
KG Jebsen Center for Cardiac Research, University of Oslo, Norway (H.P.-D., D.B.L., M.F., X.S., A.B.-D., Y.H., M.L., G.C., W.E.L.).

Tomi Tuomainen (T)

A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland (T.T., P.T.).

Pasi Tavi (P)

A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland (T.T., P.T.).

Peter P Jones (PP)

Department of Physiology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand (P.P.J.).

Marianne Lunde (M)

Institute for Experimental Medical Research (IEMR), Oslo University Hospital and University of Oslo, Norway (H.P.-D., D.B.L., M.F., C.R.C., X.S., A.B.-D., Y.H., M.L., G.C., J.P.M., W.E.L.).
KG Jebsen Center for Cardiac Research, University of Oslo, Norway (H.P.-D., D.B.L., M.F., X.S., A.B.-D., Y.H., M.L., G.C., W.E.L.).

J Andrew Wasserstrom (JA)

Northwestern University Feinberg School of Medicine, Chicago, IL (J.A.W.).

Jocelyn Laporte (J)

Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U1258, CNRS UMR7104, Strasbourg University, Illkirch, France (J.L.).

Nina D Ullrich (ND)

Division of Cardiovascular Physiology, Institute of Physiology and Pathophysiology, Heidelberg University, Germany (F.K., N.D.U.).
German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, Germany (N.D.U.).

Geir Christensen (G)

Institute for Experimental Medical Research (IEMR), Oslo University Hospital and University of Oslo, Norway (H.P.-D., D.B.L., M.F., C.R.C., X.S., A.B.-D., Y.H., M.L., G.C., J.P.M., W.E.L.).
KG Jebsen Center for Cardiac Research, University of Oslo, Norway (H.P.-D., D.B.L., M.F., X.S., A.B.-D., Y.H., M.L., G.C., W.E.L.).

J Preben Morth (JP)

Institute for Experimental Medical Research (IEMR), Oslo University Hospital and University of Oslo, Norway (H.P.-D., D.B.L., M.F., C.R.C., X.S., A.B.-D., Y.H., M.L., G.C., J.P.M., W.E.L.).
Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership University of Oslo, Norway (H.P.-D., J.P.M.).
Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark (J.P.M.).

William E Louch (WE)

Institute for Experimental Medical Research (IEMR), Oslo University Hospital and University of Oslo, Norway (H.P.-D., D.B.L., M.F., C.R.C., X.S., A.B.-D., Y.H., M.L., G.C., J.P.M., W.E.L.).
KG Jebsen Center for Cardiac Research, University of Oslo, Norway (H.P.-D., D.B.L., M.F., X.S., A.B.-D., Y.H., M.L., G.C., W.E.L.).

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