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Science 321 (5887): 372-376

Copyright © 2008 by the American Association for the Advancement of Science

Identification of SLEEPLESS, a Sleep-Promoting Factor

Kyunghee Koh,1* William J. Joiner,1* Mark N. Wu,2* Zhifeng Yue,1 Corinne J. Smith,1 Amita Sehgal1{dagger}

Abstract: Sleep is an essential process conserved from flies to humans. The importance of sleep is underscored by its tight homeostatic control. Through a forward genetic screen, we identified a gene, sleepless, required for sleep in Drosophila. The sleepless gene encodes a brain-enriched, glycosylphosphatidylinositol-anchored protein. Loss of SLEEPLESS protein caused an extreme (>80%) reduction in sleep; a moderate reduction in SLEEPLESS had minimal effects on baseline sleep but markedly reduced the amount of recovery sleep after sleep deprivation. Genetic and molecular analyses revealed that quiver, a mutation that impairs Shaker-dependent potassium current, is an allele of sleepless. Consistent with this finding, Shaker protein levels were reduced in sleepless mutants. We propose that SLEEPLESS is a signaling molecule that connects sleep drive to lowered membrane excitability.

1 Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania, Philadelphia, PA 19104, USA.
2 Division of Sleep Medicine, Department of Neurology, University of Pennsylvania, Philadelphia, PA 19104, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: amita{at}mail.med.upenn.edu

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