Epac proteins: novel therapeutic targets in heart failure – from signalosomes to drug discovery

The discovery of a family of guanine nucleotide exchange factors (GEFs) named Exchange proteins directly activated by cAMP (Epac) has opened up a new avenue of research that is beginning to explain how cAMP can mediate a wide range of biological functions. Epac are GEFs for Ras-like small GTPase family members, Rap1 and Rap2 and function in a protein kinase A independent manner. Compelling evidence is now accumulating about the formation of molecular complexes in distinct cellular compartments that influence Epac signalling and cellular function. Here we will present recent data on the role of Epac proteins and associated signalling in cardiac pathophysiology. We also highlight ongoing work into the discovery of novel pharmacological compounds targeting Epac proteins and their therapeutic potential for the treatment of cardiac diseases.