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Altered entrainment and feedback loop function effected by a mutant period protein.

P Schotland1, M Hunter-Ensor, T Lawrence

  • 1Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|January 29, 2000
PubMed
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Mutant period (per) protein, hypophosphorylated and unstable, disrupts circadian clock feedback. This affects fly behavior and light response, revealing timeless (tim) protein

Area of Science:

  • Chronobiology
  • Molecular Biology
  • Genetics

Background:

  • The circadian clock relies on interacting period (PER) and timeless (TIM) proteins.
  • PER and TIM protein levels and phosphorylation states oscillate rhythmically.
  • These proteins regulate cyclic gene expression via negative feedback.

Purpose of the Study:

  • To investigate the role of PER protein phosphorylation in circadian clock function.
  • To analyze the impact of a hypophosphorylated PER mutant on feedback mechanisms.
  • To understand the influence of PER and TIM interactions on light-induced phase shifts.

Main Methods:

  • Generated a hypophosphorylated PER mutant protein via a small internal deletion.
  • Analyzed PER protein stability and oscillation amplitude.

Related Experiment Videos

  • Assessed PER-TIM complex formation and RNA levels in transgenic flies.
  • Studied behavioral responses to temperature and light stimuli in mutant flies.

    • Main Results:

    • Hypophosphorylated PER protein exhibits increased stability and reduced oscillation amplitude.
    • Mutant PER protein shows impaired feedback repression, leading to elevated PER RNA and TIM levels.
    • Transgenic flies display temperature-dependent period shortening and altered light-response.
    • Light induces per RNA in mutant flies, suggesting TIM's direct role in transcriptional inhibition.

    Conclusions:

    • Phosphorylation is crucial for PER protein turnover and circadian rhythm regulation.
    • TIM protein plays a direct role in light-mediated transcriptional inhibition of per.
    • These findings refine models of circadian feedback loops and light-response mechanisms.