Cyclic AMP does double duty to support parallel signaling in primary cilium and cytosol

Abstract

The primary cilium maintains all of the necessary machinery to generate and interpret cAMP signals within its tiny volume, leading to the supposition that ciliary cAMP provides unique biological instructions separate from those derived from the rest of the cell body. A new paper by Truong et al. has used optogenetic and chemogenetic tricks to selectively manipulate cAMP signaling within the primary cilium. Their data show that ciliary but not cytosolic message preferentially regulates transcriptional activity via the hedgehog pathway leading to actions on zebrafish development. Computer modeling provides a rational explanation as to how the geometry of this organelle enables it to tune out cAMP signals from the cell body in order to pick up messages generated in the cilium.

Keywords: Cyclic AMP microdomain; DREADDs; Photoactivatable adenylyl cyclase bPAC; Primary cilium; Protein Kinase A; Zebrafish.