The COP9 signalosome is required for light-dependent timeless degradation and Drosophila clock resetting

Alyson Knowles, Kyunghee Koh, June Tai Wu, Cheng Ting Chien, Daniel A. Chamovitz, Justin Blau

Research output: Contribution to journalArticle

Abstract

The ubiquitin-proteasome system plays a major role in the rhythmic accumulation and turnover of molecular clock components. In turn, these ∼24 h molecular rhythms drive circadian rhythms of behavior and physiology. In Drosophila, the ubiquitin-proteasome system also plays a critical role in light-dependent degradation of the clock protein Timeless (TIM), a key step in the entrainment of the molecular clocks to light-dark cycles. Here, we investigated the role of the COP9 signalosome (CSN), a general regulator of protein degradation, in fly circadian rhythms. We found that null mutations in the genes encoding the CSN4 and CSN5 subunits prevent normal TIM degradation by light in the pacemaker lateral neurons (LNs) as does LN-specific expression of a dominant-negative CSN5 transgene. These defects are accompanied by strong reductions in behavioral phase shifts of adult flies lacking normal CSN5 activity in LNs. Defects in TIM degradation and resetting of behavioral phases were rescued by overexpression of Jetlag (JET), the F-box protein required for light-mediated TIM degradation. Flies lacking normal CSN activity in all clock neurons are rhythmic in constant light, a phenotype previously associated with jet mutants. Together, these data indicate that JET and the CSN lie in a common pathway leading to light-dependent TIM degradation. Surprisingly, we found that manipulations that strongly inhibit CSN activity had minimal effects on circadian rhythms in constant darkness, indicating a specific role for the CSN in light-mediated TIM degradation.

Original languageEnglish (US)
Pages (from-to)1152-1162
Number of pages11
JournalJournal of Neuroscience
Volume29
Issue number4
DOIs
StatePublished - Jan 28 2009

Fingerprint

Drosophila
Light
Circadian Rhythm
Diptera
Neurons
Proteasome Endopeptidase Complex
Ubiquitin
Proteolysis
F-Box Proteins
Darkness
Photoperiod
Transgenes
COP9 signalosome complex
Phenotype
Mutation
Genes

Keywords

  • Circadian rhythms
  • COP9 signalosome
  • Entrainment
  • Light signaling
  • Protein degradation
  • Timeless

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

The COP9 signalosome is required for light-dependent timeless degradation and Drosophila clock resetting. / Knowles, Alyson; Koh, Kyunghee; Wu, June Tai; Chien, Cheng Ting; Chamovitz, Daniel A.; Blau, Justin.

In: Journal of Neuroscience, Vol. 29, No. 4, 28.01.2009, p. 1152-1162.

Research output: Contribution to journalArticle

Knowles, Alyson ; Koh, Kyunghee ; Wu, June Tai ; Chien, Cheng Ting ; Chamovitz, Daniel A. ; Blau, Justin. / The COP9 signalosome is required for light-dependent timeless degradation and Drosophila clock resetting. In: Journal of Neuroscience. 2009 ; Vol. 29, No. 4. pp. 1152-1162.
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