Significance
This work describes an advance in the understanding of how the important circadian neuropeptide PDF contributes to the function of the molecular clock in
Drosophila
neurons. The famous
per
S
allele of
period
significantly improves the rhythmicity of flies missing PDF. The
per
S
gene product degrades rapidly, suggesting that PDF-mediated cAMP affects PER stability. Indeed, increasing cAMP levels and cAMP-mediated protein kinase A (PKA) activity stabilizes PER, in tissue culture cells and in circadian neurons. PDF addition to fly brains in vitro has a similar effect. Our observations taken together indicate that PDF contributes to clock neuron function by activating PKA, stabilizing PER, and thereby slowing the pace of clock neurons that respond to PDF.