SLEEPLESS, a Ly-6/neurotoxin family member, regulates the levels, localization and activity of Shaker

Mark N. Wu, William J. Joiner, Terry Dean, Zhifeng Yue, Corinne J. Smith, Dechun Chen, Toshinori Hoshi, Amita Sehgal, Kyunghee Koh

Research output: Contribution to journalArticlepeer-review

77 Scopus citations


Sleep is a whole-organism phenomenon accompanied by global changes in neural activity. We previously identified SLEEPLESS (SSS) as a glycosylphosphatidyl inositol-anchored protein required for sleep in Drosophila. Here we found that SSS is critical for regulating the sleep-modulating potassium channel Shaker. SSS and Shaker shared similar expression patterns in the brain and specifically affected each other's expression levels. sleepless (sss) loss-of-function mutants exhibited altered Shaker localization, reduced Shaker current density and slower Shaker current kinetics. Transgenic expression of sss in sss mutants rescued defects in Shaker expression and activity cell-autonomously and suggested that SSS functions in wake-promoting, cholinergic neurons. In heterologous cells, SSS accelerated the kinetics of Shaker currents and was co-immunoprecipitated with Shaker, suggesting that SSS modulates Shaker activity via a direct interaction. SSS is predicted to belong to the Ly-6/neurotoxin superfamily, suggesting a mechanism for regulation of neuronal excitability by endogenous toxin-like molecules.

Original languageEnglish (US)
Pages (from-to)69-75
Number of pages7
JournalNature neuroscience
Issue number1
StatePublished - Jan 17 2010

ASJC Scopus subject areas

  • General Neuroscience


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