Abstract

 

The well-known second messenger cyclic adenosine monophosphate (cAMP) regulates the morphology and physiology of neurons and thus higher cognitive brain functions. The discovery of an exchange protein activated by cAMP (Epac) as a guanine-nucleotide exchange factor for Rap GTPases has shed light on protein kinase A (PKA)-independent functions of cAMP signaling in neural tissues. Studies of cAMP-Epac-mediated signaling in neurons under normal and disease conditions also revealed its diverse contributions to neurodevelopment, synaptic remodeling, neurotransmitter release, learning, memory, and emotion. This mini-review summarizes the various roles of Epac isoforms, including Epac1 and Epac2, which are highly expressed in neural tissues, and highlights issues that need to be resolved in order to uncover the critical functions of Epac in neural tissues and the potential for a new therapeutic target of mental disorders.