Response of the timeless protein to light correlates with behavioral entrainment and suggests a nonvisual pathway for circadian photoreception

Neuron. 1998 Jul;21(1):215-23. doi: 10.1016/s0896-6273(00)80528-0.


The period (per) and timeless (tim) genes are required for circadian behavioral rhythms in Drosophila. The current model for how these rhythms entrain to light is based upon the light induced decrease in timeless protein (TIM) levels. We show here that the TIM response to light correlates with the effect of light on the behavioral rhythm. To identify components of the entrainment pathway, we also assayed the TIM response in flies with mutant visual systems. Flies that lacked eyes displayed a normal response in lateral neurons. The TIM response to a light pulse was attenuated in flies that were mutant for the transient receptor potential (trp) and trp-like (trpl) genes, which are required for calcium conductance in the visual transduction cascade. The reduced TIM response was accompanied by a reduced phase shift in the behavioral rhythm, but neither response was completely eliminated, and the trpl;trp flies entrain to light-dark cycles, suggesting that these genes perturb some aspect of circadian entrainment when mutated but are not essential for it. The TIM response was also unaffected in ninaE flies that lack the rhodopsin protein (rh1). These results support the hypothesis that circadian entrainment does not rely on the visual system and likely involves a dedicated pathway for photoreception.

Publication types

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

MeSH terms

  • Animals
  • Behavior, Animal / physiology*
  • Calcium Channels / genetics
  • Circadian Rhythm / physiology*
  • Dose-Response Relationship, Radiation
  • Drosophila / genetics
  • Drosophila Proteins*
  • Eye Abnormalities / genetics
  • Eye Abnormalities / physiopathology
  • Eye Proteins / genetics
  • Insect Proteins / radiation effects*
  • Light*
  • Mutation / physiology
  • Neurons / metabolism
  • Neurons / radiation effects
  • Photoreceptor Cells, Invertebrate / physiology*
  • Reference Values
  • Rhodopsin
  • TRPC Cation Channels


  • Calcium Channels
  • Drosophila Proteins
  • Eye Proteins
  • Insect Proteins
  • TRPC Cation Channels
  • ninaE protein, Drosophila
  • tim protein, Drosophila
  • transient receptor potential cation channel, subfamily C, member 1
  • Rhodopsin