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Activation of EGFR and ERK by rhomboid signaling regulates the consolidation and maintenance of sleep in Drosophila

Nature Neuroscience volume 10, pages 1160–1167 (2007)Cite this article

Abstract

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 fly 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.

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Figure 1: Increased sleep during day and night after activation of EGFR.
Figure 2: Dose-dependent increase in sleep after overexpression of Rho or Rho and Star.
Figure 3: Reduced sleep after directed rho-RNAi expression.
Figure 4: Increased sleep in c767, 50Y and c687 flies overexpressing EGFR ligand.
Figure 5: Lack of circadian shift after inhibition of sleep with rhoDN.
Figure 6: Increased sleep correlated with increased levels of ppERK.
Figure 7: Rho is expressed in pars intercerebralis (PI) cells.

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Acknowledgements

We dedicate this paper to the memory of our mentor, colleague and friend, John Newport, who died 25 December 2005. We thank A. Guichard for essential technical guidance and advice, E. J. Kim and J. Wagner for technical assistance, M. Kaneko, R. Andretic, H. Dierick, P. Shaw, C.P. Kyriacou, E. Green, T. Roenneberg and M. Merrow for assistance with data analysis, and E. Bier, J. Wang, W. McGinnis, R. Andretic, M. Kaneko and H. Dierick for comments on the manuscript. This work was supported by a US National Institutes of Health grant (J.W.N.) and a US National Science Foundation grant No. 0432063 (R.J.G.). R.J.G. is the Dorothy and Lewis B. Cullman Fellow at the Neurosciences Institute, which is supported by the Neurosciences Research Foundation.

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  1. John W Newport: Deceased.

Authors and Affiliations

  1. Department of Biology, University of California San Diego, 9500 Gilman Dr., La Jolla, 92093, California, USA

    Krisztina Foltenyi & John W Newport

  2. The Neurosciences Institute, 10640 John Jay Hopkins Dr., San Diego, 92121, California, USA

    Krisztina Foltenyi & Ralph J Greenspan

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  1. Krisztina Foltenyi
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Correspondence to Ralph J Greenspan.

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Foltenyi, K., Greenspan, R. & Newport, J. Activation of EGFR and ERK by rhomboid signaling regulates the consolidation and maintenance of sleep in Drosophila. Nat Neurosci 10, 1160–1167 (2007). https://doi.org/10.1038/nn1957

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