Proteomics

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


ABSTRACT: 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.

INSTRUMENT(S): LTQ Orbitrap Elite, Q Exactive

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Heart, Regular Ventricular Cardiac Myocyte, Fetal Cardiomyocyte

DISEASE(S): Disease Free

SUBMITTER: Duangnapa Kovanich  

LAB HEAD: Manuela Zaccolo

PROVIDER: PXD033773 | Pride | 2023-03-10

REPOSITORIES: Pride

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Publications


<h4>Background</h4>Signaling by cAMP is organized in multiple distinct subcellular nanodomains regulated by cAMP-hydrolyzing PDEs (phosphodiesterases). Cardiac β-adrenergic signaling has served as the prototypical system to elucidate cAMP compartmentalization. Although studies in cardiac myocytes have provided an understanding of the location and properties of a handful of cAMP subcellular compartments, an overall view of the cellular landscape of cAMP nanodomains is missing.<h4>Methods</h4>Here  ...[more]

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