BIN1, Myotubularin, and Dynamin-2 Coordinate T-Tubule Growth in Cardiomyocytes.
Animals
Humans
Mice
Adaptor Proteins, Signal Transducing
/ genetics
Dynamin II
/ genetics
Myocytes, Cardiac
/ metabolism
Nerve Tissue Proteins
/ metabolism
Nuclear Proteins
/ metabolism
Protein Isoforms
/ metabolism
Protein Tyrosine Phosphatases, Non-Receptor
/ genetics
Tumor Suppressor Proteins
/ metabolism
BIN1
cardiomyocyte
dynamin II
myotubularin
t-tubule
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
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