A role of SIFa and its receptor SIFR on sleep in Drosophila melanogaster

Abstract

Recent researches have now shown that sleep contributes to maintain homeostasis such as memory consolidation, energy storage, restoration and etc. However, most of the details of sleep regulatory mechanism still need to be studied. During the last decade, sleep research has been undertaken using Drosophila as a model organism. So far, there are about 30 genes and neurotransmitters which control the sleep process, and novel ones are found continuously. In this research, we found SIF-amide receptor and its ligand SIF-amide as novel regulators of sleep SIFa is one of 40 neurotransmitters and hormones already known in Drosophila. Its function, reported till now, is regulating sexual behavior such as preference for opposite sex during mating. It is expressed in the pars intercerebralis (PI) region of brain and projects to antennal lobe (AL), fan-shaped body (FB), and etc. for signal transmission. SIFR, a GPCR of Drosophila reactive against SIFa, has not been researched actively. It is supposed to correlate thermo-nociception and lifespan, but we do not know how it works. Hypomorph mutants or down-regulated mutants by RNAi of SIFR show shorter sleep duration than wild type. Using brain region specific GAL4 screening, we found that SIFR regulates sleep in the PI region, the homologue of mammalian hypothalamus. Moreover, when SIFa, the ligand of SIFR, is knocked down, flies show decreased sleep length like when SIFR is knocked down. SIFa neuron also modulates sleep process. When Tetanus toxin is misexpressed in SIFa neuron to block the transmission of neurotransmitters, the mutant shows short sleep phenotype. This result is same as SIFa knock-down mutant fly. On the other hand, we tested the relevance of sleep and circadian rhythm to SIFR and SIFa mutants. SIFR and SIFa down-regulated mutant shows no change in circadian rhythm. Therefore, SIFR and SIFa only control the sleep process in Drosophila. Eventually, SIF-amide secretory neurons in the PI transfer the signals ...