A role for the segment polarity gene shaggy/GSK-3 in the Drosophila circadian clock

Cell. 2001 Jun 15;105(6):769-79. doi: 10.1016/s0092-8674(01)00383-x.

Abstract

Tissue-specific overexpression of the glycogen synthase kinase-3 (GSK-3) ortholog shaggy (sgg) shortens the period of the Drosophila circadian locomotor activity cycle. The short period phenotype was attributed to premature nuclear translocation of the PERIOD/TIMELESS heterodimer. Reducing SGG/GSK-3 activity lengthens period, demonstrating an intrinsic role for the kinase in circadian rhythmicity. Lowered sgg activity decreased TIMELESS phosphorylation, and it was found that GSK-3 beta specifically phosphorylates TIMELESS in vitro. Overexpression of sgg in vivo converts hypophosphorylated TIMELESS to a hyperphosphorylated protein whose electrophoretic mobility, and light and phosphatase sensitivity, are indistinguishable from the rhythmically produced hyperphosphorylated TIMELESS of wild-type flies. Our results indicate a role for SGG/GSK-3 in TIMELESS phosphorylation and in the regulated nuclear translocation of the PERIOD/TIMELESS heterodimer.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Biological Clocks / genetics
  • Biological Clocks / physiology*
  • Cell Nucleus / metabolism
  • Circadian Rhythm / genetics
  • Circadian Rhythm / physiology*
  • Dimerization
  • Drosophila Proteins*
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / physiology*
  • Glycogen Synthase Kinase 3*
  • Immunoblotting
  • Insect Proteins / genetics
  • Insect Proteins / metabolism*
  • Microscopy, Fluorescence
  • Motor Activity / genetics
  • Motor Activity / physiology
  • Nuclear Proteins / metabolism*
  • Period Circadian Proteins
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA / genetics
  • RNA / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism

Substances

  • Drosophila Proteins
  • Insect Proteins
  • Nuclear Proteins
  • PER protein, Drosophila
  • Period Circadian Proteins
  • Recombinant Fusion Proteins
  • tim protein, Drosophila
  • RNA
  • Protein-Serine-Threonine Kinases
  • Sgg protein, Drosophila
  • Glycogen Synthase Kinase 3