Gunasekaran Subramaniam, Katharina Schleicher, Duangnapa Kovanich, Anna Zerio, Milda Folkmanaite, Ying-Chi Chao, Nicoletta C Surdo, Andreas Koschinski, Jianshu Hu, Arjen Scholten, Albert J R Heck, Maria Ercu, Anastasiia Sholokh, Kyung Chan Park, Enno Klussmann, Viviana Meraviglia, Milena Bellin, Sara Zanivan, Svenja Hester, Shabaz Mohammed, Manuela Zaccolo
BACKGROUND: 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. METHODS: Here, we combined an integrated phosphoproteomics approach that takes advantage of the unique role that individual PDEs play in the control of local cAMP, with network analysis to identify previously unrecognized cAMP nanodomains associated with β-adrenergic stimulation...
March 8, 2023: Circulation Research