Heart failure & cardiomyopathies
Ptpn23 Controls Cardiac T-Tubule Patterning by Promoting the Assembly of Dystrophin-Glycoprotein Complex
Authors' conclusion
Ptpn23 is essential for cardiac T-tubule formation and maintenance along Z-discs. During postnatal heart development, Ptpn23 interacts with sarcomeric α-actinin and coordinates the assembly of the DGC at costameres to sculpt T-tubule spatial patterning and morphology.
Study context
- Population
- Cardiomyocyte-specific Ptpn23 and Actn2 knockout mice, dystrophin global knockout mice (DmdE4*); failing hearts from dilated cardiomyopathy patients
Main finding
As reported in the abstract
- Ptpn23 expression reduced in failing hearts from dilated cardiomyopathy patients and mice
- Ptpn23 deletion: disorganized transverse tubules (T-tubules) with enlarged diameters and progressive dilated cardiomyopathy, sarcomere organization unaffected
- Mosaic somatic mutagenesis: cell-autonomous role of Ptpn23 in T-tubule formation
- Ptpn23 essential for costamere integrity via interactions with α-actinin and dystrophin
- α-actinin deletion altered subcellular localization of Ptpn23 and dystrophin-glycoprotein complex (DGCs)
- Dystrophin inactivation caused T-tubule defects similar to Ptpn23 loss, Ptpn23 Z-disc localization unaffected
- Inducible Ptpn23 knockout at 1 month: Ptpn23 required for T-tubule maintenance in adult cardiomyocytes
Original publication
Ptpn23 Controls Cardiac T-Tubule Patterning by Promoting the Assembly of Dystrophin-Glycoprotein Complex. Circulation. Published 12 January 2024. doi:10.
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