UC Davis

Nutrient-dependent post-translational modifications (PTMs) bridge animal circadian clock and metabolism. Previous studies showed that daily cycling of protein OGlcNAcylation, a sugar-derived PTM, is driven by circadian clocks and can feedback to reinforce clock functions and daily biological rhythms. Like O-GlcNAcylation, Spalmitoylation is also a dynamic and nutrient-dependent PTM. High fat diet and palmitate treatment that may potentially affect protein S-palmitoylation are known to impact the functions of circadian clocks. I therefore hypothesize that S-palmitoylation is also a nutrient-dependent PTM underlying the interplay between metabolism and circadian clocks to regulate daily biological rhythms. Using Drosophila as an animal model, I identified many S-palmitoylation regulators with clock-controlled expression at the transcript level, suggesting that S-palmitoylation of some cellular proteins may be a clockmediated process. Among them, CG1407 that codes for a palmitoyltransferase exhibits 24-hour cycles robustly. I knocked down CG1407 genetically using RNA interference and observed the slowing down of the circadian clock and impact on daily activity rhythm. Overall, my results suggest that protein S-palmitoylation could be important for regulating daily biological rhythms. My results also highlight the utility of manipulating CG1407 expression as an experimental tool to study the interplay between S-palmitoylation cycling and biological rhythms.