An ecdysone-responsive nuclear receptor regulates circadian rhythms in Drosophila

Abstract

SummaryLittle is known about molecular links between circadian clocks and steroid hormone signaling although both are important for normal physiology. Here we report a circadian function for a nuclear receptor, Ecdysone Induced Protein 75 (Eip75/E75), which we identify through a gain-of-function screen for circadian genes in Drosophila melanogaster. Overexpression or knockdown of E75 in clock neurons disrupts rest:activity rhythms and dampens molecular oscillations. E75 represses expression of the gene encoding the transcriptional activator, CLOCK (CLK), and may also affect circadian output. PER inhibits the activity of E75 on the Clk promoter, thereby providing a mechanism for a previously proposed de-repressor effect of PER on Clk transcription. The ecdysone receptor is also expressed in central clock cells and manipulations of its expression produce effects similar to those of E75 on circadian rhythms. We find that E75 protects rhythms under stressful conditions, suggesting a function for steroid signaling in the maintenance of circadian rhythms in Drosophila.

Nuclear receptor ecdysone‐induced protein 75 is required for larval–pupal metamorphosis in the Colorado potato beetle Leptinotarsa decemlineata (Say)

“…In T. domestica, RNAi-mediated knockdown of TdE75 considerably altered the rhythmic transcription of Cyc and Tim (Kamae et al, 2014). Similarly, DmE75 represses DmClk expression, and may also affect circadian output in D. melanogaster (Kumar et al, 2014). In the present study, knockdown of all three of the LdE75 isoforms may disturb the circadian clock and negatively affects ecdysone production and release in L. decemlineata.…”

“…Similarly, Dm E75 represses DmClk expression, and may also affect circadian output in D . melanogaster (Kumar et al ., ). In the present study, knockdown of all three of the LdE75 isoforms may disturb the circadian clock and negatively affects ecdysone production and release in L. decemlineata .…”

TRAP-seq Profiling and RNAi-Based Genetic Screens Identify Conserved Glial Genes Required for Adult Drosophila Behavior

“…To our knowledge there is no evidence of local ecdysteroid synthesis in the fly nervous system, but receptors for the hormone (nuclear hormone receptors) are present in this tissue (Truman et al, 1994). Moreover, clock neurons themselves express ecdysteroid-responsive nuclear hormone receptors (e.g., UNF and E75), as well as a membrane ABC transporter (E23) postulated to regulate hormone responsiveness, and these are required for normal circadian rhythmicity (Itoh et al, 2011; Kumar et al, 2014; Jaumouillè et al, 2015). Evidence suggests that these factors serve as components of the molecular clock in Drosophila and more primitive insects (Kamae et al, 2014); they may respond to hormone to regulate specific genes, the molecular clock and behavior.…”

Conserved and Exapted Functions of Nuclear Receptors in Animal Development

“…In Drosophila males, E75 promotes stem cell maintenance in the testis, and knockdown causes a loss of germ stem cells and cyst stem cells [23]. The final known role of E75 in Drosophila is similar to that of its mammalian ortholog, Rev-Erb : E75 functions in the fly molecular clock and circadian rhythm in clock and pacemaker neurons [24]. E75 and unf (see below) act together to enhance transcription of per , which finishes the transcriptional feedback loop needed for rhythmic cycles of gene expression within cells [19].…”