Spatial and temporal crosstalk between the cAMP and Ca signaling systems.

The ubiquitous secondary messengers, Ca and cAMP, play a vital role in shaping a diverse array of physiological processes. More significantly, accumulating evidence over the past several decades underpin extensive crosstalk between these two canonical messengers in discrete sub-cellular nanodomains across various cell types. Within such specialized nanodomains, each messenger fine-tunes signaling to maintain homeostasis by manipulating the activities of cellular machinery accountable for the metabolism or activity of the complementary pathway. Interaction between these messengers is ensured by scaffolding proteins which tether components of the signaling machinery in close proximity. Disruption of dynamic communications between Ca and cAMP at these loci consequently is linked to several pathological conditions. This review summarizes recent novel mechanisms underlying effective crosstalk between Ca and cAMP in such nanodomains.