Antagonistic Regulation of Circadian Output and Synaptic Development by the E3 Ubiquitin Ligase JETLAG and the DYSCHRONIC-SLOWPOKE Complex

Circadian output genes act downstream of the clock to promote rhythmic changes in behavior and physiology, yet their molecular and cellular functions are not well understood. Here we characterize an interaction between regulators of circadian entrainment, output and synaptic development in Drosophila that influences clock-driven anticipatory increases in morning and evening activity. We previously showed the JETLAG (JET) E3 Ubiquitin ligase resets the clock upon light exposure, while the PDZ protein DYSCHRONIC (DYSC) regulates circadian locomotor output and synaptic development. Surprisingly, we find that JET and DYSC antagonistically regulate synaptic development at the larval neuromuscular junction, and reduced JET activity rescues arrhythmicity of dysc mutants. Consistent with our prior finding that DYSC regulates SLOWPOKE (SLO) potassium channel expression, jet mutations also rescue circadian and synaptic phenotypes in slo mutants. Collectively, our data suggest that JET, DYSC and SLO promote circadian output in part by regulating synaptic morphology.\n\nHighlightsO_LILoss of DYSC differentially impacts morning and evening oscillators\nC_LIO_LIReduced JET activity rescues the dysc and slo arrhythmic phenotype\nC_LIO_LIReduced JET activity causes synaptic defects at the larval NMJ\nC_LIO_LIJET opposes DYSC and SLO function at the NMJ synapse\nC_LI