Cellular Dissection of Circadian Peptide Signals with Genetically Encoded Membrane-Tethered Ligands

t-peptides induce activation of their cognate GPCRs in cells expressing both the t-peptide and its receptor.

• Activation of the pigment-dispersing factor (PDF) receptor (PDFR) is crucial for intercellular communication and coordination of clock neuron activity in Drosophila melanogaster.
• Broad expression of t-PDF can restore rhythmicity in flies lacking the PDF gene (pdf(01) null mutation).
• t-PDF activation likely stimulates PDFR in clock neurons that do not secrete PDF themselves.
• More localized expression of t-PDF appears to influence the timing of cellular rhythms, with some neurons accelerating and others decelerating.
• The findings suggest a specific role for PDF signaling in circadian control that operates independently of intercellular phase information transfer.

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