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http://www.nature.com/natureneuroscience
Web End = Activation of EGFR and ERK by rhomboid signaling regulates the consolidation and maintenance of sleep in Drosophila
http://www.nature.com/natureneuroscience
Nature Publishing Group
200 7
Krisztina Foltenyi1,2, Ralph J Greenspan2 & John W Newport1,3
Epidermal growth factor receptor (EGFR) signaling in the mammalian hypothalamus is important in the circadian regulation of activity. We have examined the role of this pathway in the regulation of sleep in Drosophila melanogaster. Our results demonstrate that rhomboid (Rho)- and Star-mediated activation of EGFR and ERK signaling increases sleep in a dose-dependent manner, and that blockade of rhomboid (rho) expression in the nervous system decreases sleep. The requirement of rho for sleep localized to the pars intercerebralis, a part of the y brain that is developmentally and functionally analogous to the hypothalamus in vertebrates. These results suggest that sleep and its regulation by EGFR signaling may be ancestral to insects and mammals.
The function of sleep remains elusive and there is scant information about the signaling transduction pathways that are involved in it. In recent years, the development of a promising model system in Drosophila has yielded evidence that the fruit y shows the canonical hallmarks of sleep, as previously dened in mammals. The sleep state includes consolidated periods of inactivity, an increased arousal threshold, and a homeostatic drive to recover sleep after deprivation1,2.
Furthermore, Drosophila responds to the same pharmacological agents that are known to modulate arousal in mammals2,3, and sleep levels
in Drosophila decline and become fragmented with age4. Here we have shown the role of a classical signaling pathway, common to both ies and mammals, that further supports the power of the y model system for discovering the molecular modulators of sleep in their anatomical context.
Rhythmic transcription and secretion in the suprachiasmatic nucleus (SCN) of transforming growth factora (TGF-a), a ligand for the EGFR (or ErbB-1 in mammals), produces rhythmic behaviors, including sleep. These become irregular in response to the elimination of the rhythmicity of SCN TGF-a secretion, or with the use of a hypomorphic Egfr allele5. Although the ErbB family of receptor tyrosine kinases may have a role in the endogenous regulation of sleep6, no direct evidence for this exists. We have addressed this question in Drosophila, where the ErbB family is...