Figure 9. A model for a circadian signalosome comprised of preferential PDF-R:AC3:nervy coupling.

M pacemakers respond to dopamine, DH31, and PDF-R through G_sα-coupled receptors: Activation of each receptor lead to increases in cAMP levels. Both DH31 and PDF receptors signal through G_sα60A, however AC3 alterations affect PDF signaling without affecting DH31 responses. We propose that PDF signals through AC3 to affect circadian function but that dopamine and DH31 couple to other AC isoforms. Likewise, the AKAP nervy preferentially associates with the PDF-R:AC3 signaling complex; other AKAPs support the G_sα-coupled receptors that mediate responsiveness to DA and DH31.