Identification of SLEEPLESS, a sleep-promoting factor

被引:231
作者
Koh, Kyunghee [1 ]
Joiner, William J. [1 ]
Wu, Mark N. [2 ]
Yue, Zhifeng [1 ]
Smith, Corinne J. [1 ]
Sehgal, Amita [1 ]
机构
[1] Univ Penn, Howard Hughes Med Inst, Dept Neurosci, Philadelphia, PA 19104 USA
[2] Univ Penn, Div Sleep Med, Dept Neurol, Philadelphia, PA 19104 USA
关键词
D O I
10.1126/science.1155942
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:372 / 376
页数:5
相关论文
共 37 条
[11]   Regulated cleavage of a contact-mediated axon repellent [J].
Hattori, M ;
Osterfield, M ;
Flanagan, JG .
SCIENCE, 2000, 289 (5483) :1360-1365
[12]   Rest in Drosophila is a sleep-like state [J].
Hendricks, JC ;
Finn, SM ;
Panckeri, KA ;
Chavkin, J ;
Williams, JA ;
Sehgal, A ;
Pack, AI .
NEURON, 2000, 25 (01) :129-138
[13]   Gender dimorphism in the role of cycle (BMAL1) in rest, rest regulation, and longevity in Drosophila melanogaster [J].
Hendricks, JC ;
Lu, SM ;
Kume, K ;
Yin, JCP ;
Yang, ZH ;
Sehgal, A .
JOURNAL OF BIOLOGICAL RHYTHMS, 2003, 18 (01) :12-25
[14]  
Hu WP, 2007, SLEEP, V30, P247
[15]   Effects of sleep deprivation on sleep and sleep EEG in three mouse strains: empirical data and simulations [J].
Huber, R ;
Deboer, T ;
Tobler, I .
BRAIN RESEARCH, 2000, 857 (1-2) :8-19
[16]   Sleep homeostasis in Drosophila melanogaster [J].
Huber, R ;
Hill, SL ;
Holladay, C ;
Biesiadecki, M ;
Tononi, G ;
Cirelli, C .
SLEEP, 2004, 27 (04) :628-639
[17]   Genetic analysis of oxygen defense mechanisms in Drosophila melanogaster and identification of a novel behavioural mutant with a Shaker phenotype [J].
Humphreys, JM ;
Duyf, B ;
Joiner, MLA ;
Phillips, JP ;
Hilliker, AJ .
GENOME, 1996, 39 (04) :749-757
[18]   Mutations in Rab3a alter circadian period and homeostatic response to sleep loss in the mouse [J].
Kapfhamer, D ;
Valladares, O ;
Sun, Y ;
Nolan, PM ;
Rux, JJ ;
Arnold, SE ;
Veasey, SC ;
Bucan, M .
NATURE GENETICS, 2002, 32 (02) :290-295
[19]   Regulation of daily locomotor activity and sleep by hypothalamic EGF receptor signaling [J].
Kramer, A ;
Yang, FC ;
Snodgrass, P ;
Li, XD ;
Scammell, TE ;
Davis, FC ;
Weitz, CJ .
SCIENCE, 2001, 294 (5551) :2511-2515
[20]   Dopamine is a regulator of arousal in the fruit fly [J].
Kume, K ;
Kume, S ;
Park, SK ;
Hirsh, J ;
Jackson, FR .
JOURNAL OF NEUROSCIENCE, 2005, 25 (32) :7377-7384