Heart failure & cardiomyopathies
Unique Role of Intracellular Perinuclear β 1 -Adrenergic Receptors in Defining Signaling Compartmentation and Pathological Cardiac Remodeling
Authors' conclusion
These results demonstrate that β1ARs localized to Golgi membranes facing the outer nuclear membrane regulate A-kinase anchoring protein 6β signalosomes required for the induction of pathological cardiac remodeling, defining an intracellular nanocompartment.
Study context
- Population
- Rat and human cardiomyocytes; wild-type mice and a mouse model of familial dilated cardiomyopathy
Main finding
As reported in the abstract
- Intracellular β1ARs on Golgi membrane facing the outer nuclear membrane regulate a perinuclear cAMP compartment (AKAP6β signalosome), selectively regulating perinuclear PKA activity independently of plasma membrane or endosomal βARs
- AKAP6β compartment is nanometer scale and depends on local restriction of cAMP diffusion
- Perinuclear βARs sufficient and necessary for calcineurin-NFAT pathway activation and myocyte hypertrophy in vitro
- AAV9 delivery of outer nuclear membrane-localized pepducin activating perinuclear βARs induced dilated cardiomyopathy in wild-type mice
- In vivo outer nuclear membrane-localized nanobody inhibiting perinuclear βARs improved cardiac function and inhibited pathological remodeling in familial dilated cardiomyopathy mice with established disease
Original publication
Unique Role of Intracellular Perinuclear β 1 -Adrenergic Receptors in Defining Signaling Compartmentation and Pathological Cardiac Remodeling. Circulation. Published 16 July 2025. doi:10.
Summarised from the published abstract; every number is checked against it