Integrated proteomics unveils regulation of cardiac myocytes hypertrophic growth by a nuclear cAMP nanodomain under the control of PDE3A

Signalling by cAMP is organized in multiple distinct subcellular nanodomains regulated by cAMP-hydrolysing phosphodiesterase (PDEs). Cardiac b-adrenergic signalling has served as the prototypical system to elucidate cAMP compartmentalization. Here we employed an integrated interaction and phosphoproteomics approaches that take advantage of the unique role that individual PDEs play in the control of local cAMP to identify previously unrecognizedncAMP nanodomains associated with b-adrenegic stimulation. The characterization of one such domain demonstrated that PDE3A isoforms operate in a nuclear nanodomain that involves SMAD4 and HDAC-1 to inhibit cardiac myocyte hypertrophic growth.