Direct visualization of cAMP signaling in primary cilia reveals up-regulation of ciliary GPCR activity following Hedgehog activation

Significance The primary cilium, a small organelle essential to normal development, has recently been thrust into the limelight owing to its involvement in adult disease states such as cancer, obesity, neurodegeneration, and polycystic kidney disease. Here we developed optical approaches to interrogate the function of receptors that work through cAMP-PKA signaling within the primary cilium of live cells. Our data provide a key piece of the puzzle concerning the way in which localized cAMP signals regulate the Hedgehog pathway, another ciliary signaling system with emerging roles in multiple disease processes.