STKE: Knitting a Ravelled Sleave

Science  14 Sep 2007:
Vol. 317, Issue 5844, pp. 1473c
DOI: 10.1126/science.317.5844.1473c

For an activity in which we spend a third of our lives, much about sleep remains enigmatic. Foltenyi et al. investigated the role of epidermal growth factor receptor (EGFR) signaling in regulating sleep in Drosophila. In the fly, the activation of EGFR ligands such as Spitz depends on the transmembrane protein Star and on Rhomboid family (Rho) proteases. Using flies in which Rho and Star expression could be conditionally induced, they showed that overexpression led to a transient increase in both the duration and number of sleep episodes, which was followed by a decrease and then a return to normal. The overexpression of Rho and Star also led to an increase in phosphorylation of extracellular signal-regulated kinase (ERK, a target of EGFR signaling) that paralleled the temporal pattern of increased sleep, and the increase in ERK phosphorylation was greatest in the tritocerebrum. Moreover, several lines of flies in which Rho activity in neurons projecting from the pars intercerebralis (PI, a region analogous to the vertebrate hypothalamus) to the tritocerebrum was inhibited with RNA interference showed decreased sleep. This decrease involved brief sleep episodes in conjunction with an increase in the number of times that sleep was attempted—potentially a fly model of insomnia. The authors propose that the production of EGFR ligand by PI neurons leads to ERK activation in tritocerebrum neurons, thereby promoting sleep. — EMA

Nat. Neurosci. 10, 1160 (2007).

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