PRKA/PKA signals and autophagy: space matters.

Macroautophagy/autophagy is the cellular process responsible for the elimination and recycling of aggregated proteins and damaged organelles. Whereas autophagy is strictly regulated by several signaling cascades, the link between this process and the subcellular distribution of its regulatory pathways remains to be established. Our recent work suggests that the compartmentalization of PRKA/PKA (protein kinase cAMP-activated) determines its effects on autophagy. We found that increased cAMP levels generate dramatically different PRKA activity "signatures" mainly dependent on the actions of phosphatases and the distribution of the PRKA holoenzymes containing type II regulatory subunits (PRKAR2A and PRKAR2B; RII). In this punctum we discuss how compartmentalized PRKA signaling events are generated and affect the autophagic flux in specific cell types.