cAMP/PKA signaling compartmentalization in cardiomyocytes: Lessons from FRET-based biosensors

Abstract

3',5'-cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger produced in response to the stimulation of G protein-coupled receptors (GPCRs). It regulates a plethora of pathophysiological processes in different organs, including the cardiovascular system. It is now clear that cAMP is not uniformly distributed within cardiac myocytes but confined in specific subcellular compartments where it modulates key players of the excitation-contraction coupling as well as other processes including gene transcription, mitochondrial homeostasis and cell death. This review will cover the major cAMP microdomains in cardiac myocytes. We will describe recent work using pioneering tools developed for investigating the organization and the function of the major cAMP microdomains in cardiomyocytes, including the plasma membrane, the sarcoplasmic reticulum, the myofilaments, the nucleus and the mitochondria.

Keywords: Biosensor; Compartmentalization; Cyclic AMP; FRET; Microdomain.