CULLIN-3 controls TIMELESS oscillations in the Drosophila circadian clock

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Single-cell Resolution Fluorescence Live Imaging of Drosophila Circadian Clocks in Larval Brain Culture
07:05

Single-cell Resolution Fluorescence Live Imaging of Drosophila Circadian Clocks in Larval Brain Culture

Published on: January 19, 2018

Brigitte Grima1, Alexandre Dognon, Annie Lamouroux

  • 1Institut de Neurobiologie Alfred Fessard, CNRS UPR3294, Gif-sur-Yvette, France.

Plos Biology
|August 11, 2012
PubMed

Insights

Cullin-3 (CUL-3) is a newly identified component of the Drosophila circadian clock. This protein is essential for regulating PERIOD (PER) and TIMELESS (TIM) protein oscillations, impacting daily rhythms.

Area of Science:

  • Chronobiology
  • Molecular Biology
  • Genetics

Background:

  • Eukaryotic circadian clocks utilize transcriptional feedback loops for daily rhythm regulation.
  • In Drosophila, PERIOD (PER) and TIMELESS (TIM) protein oscillations are crucial for circadian timing.
  • Post-translational modifications, including phosphorylation and ubiquitination, control PER and TIM protein stability.

Purpose of the Study:

  • To investigate the role of CULLIN-3 (CUL-3) in the Drosophila circadian clock.
  • To determine how CUL-3 influences the oscillations of PER and TIMELESS (TIM) proteins.
  • To elucidate the relationship between CUL-3, SLMB, and clock protein regulation.

Main Methods:

  • RNA interference (RNAi) and dominant-negative approaches to disrupt CUL-3 function in Drosophila clock neurons.
  • Assessment of locomotor behavior under light-dark cycles and constant conditions.
  • Analysis of PER and TIM protein cycling and accumulation using Western blotting or similar techniques.
  • Co-immunoprecipitation assays to study protein complex formation.

Main Results:

  • CUL-3 disruption alters locomotor behavior and dampens PER and TIM oscillations in light-dark cycles.
  • In constant conditions, CUL-3 deregulation leads to behavioral arrhythmicity and abolishes TIM cycling, with slower effects on PER.
  • CUL-3 interacts with hypo-phosphorylated TIM, while SLMB interacts with phosphorylated TIM, indicating distinct roles.
  • CUL-3 and SLMB exhibit additive effects on PER and TIM, suggesting complementary functions in ubiquitination.

Conclusions:

  • CULLIN-3 (CUL-3) is a novel component of the Drosophila circadian clock.
  • CUL-3 plays a significant role in controlling TIMELESS (TIM) oscillations, independent of PER in some contexts.
  • Distinct ubiquitination complexes, CUL-3 and SLMB, have specialized roles in regulating clock protein turnover and circadian rhythmicity.

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