Regulation of the Drosophila Protein Timeless Suggests a Mechanism for Resetting the Circadian Clock by Light

Circadian behavioral rhythms in Drosophila depend on the appropriate regulation of at least two genes, period (per) and timeless (tim). Previous studies demonstrated that levels of PER and TIM RNA cycle with the same phase and that the PER and TIM proteins interact directly. Here we show the cyclic expression of TIM protein in adult heads and report that it lags behind peak levels of TIM RNA by several hours. We alsoshow that nuclear expression of TIM depends upon the expression of PER protein. Finally, we report that the expression of TIM, but not PER, is rapidly reduced by light, suggesting that TIM mediates light-induced resetting of the circadian clock. Since both PER and TIM RNA are unaffected by light treatment, the effects of light on TIM appear to be posttranscriptional.

[1]  M. Rosbash,et al.  PAS is a dimerization domain common to Drosophila Period and several transcription factors , 1993, Nature.

[2]  Jeffrey C. Hall,et al.  A promoterless period gene mediates behavioral rhythmicity and cyclical per expression in a restricted subset of the drosophila nervous system , 1994, Neuron.

[3]  J. F. Feldman,et al.  Isolation of circadian clock mutants of Neurospora crassa. , 1973, Genetics.

[4]  Jeffrey C. Hall,et al.  Antibodies to the period gene product of drosophila reveal diverse tissue distribution and rhythmic changes in the visual system , 1988, Neuron.

[5]  S. Shiga,et al.  Pigment‐dispersing hormone‐like peptide in the nervous system of the flies Phormia and Drosophila: Immunocytochemistry and partial characterization , 1993, The Journal of comparative neurology.

[6]  C. Strayer,et al.  Circadian clock mutants in Arabidopsis identified by luciferase imaging , 1995, Science.

[7]  Jennifer J. Loros,et al.  Light-induced resetting of a circadian clock is mediated by a rapid increase in frequency transcript , 1995, Cell.

[8]  M. Rosbash,et al.  Temporal phosphorylation of the Drosophila period protein. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[9]  M. W. Young,et al.  Suppression of PERIOD protein abundance and circadian cycling by the Drosophila clock mutation timeless. , 1995, The EMBO journal.

[10]  A. Eskin,et al.  Identification and physiology of circadian pacemakers. Introduction. , 1979, Federation proceedings.

[11]  A. Sehgal,et al.  Isolation of timeless by PER Protein Interaction: Defective Interaction Between timeless Protein and Long-Period Mutant PERL , 1995, Science.

[12]  M. Hotz Vitaterna.  Mutagenesis and mapping of a mouse gene,Clock, essential for circadian behavior , 1994 .

[13]  M. Rosbash,et al.  Circadian fluctuations of period protein immunoreactivity in the CNS and the visual system of Drosophila , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[14]  J. C. Hall,et al.  Expression of the period clock gene within different cell types in the brain of Drosophila adults and mosaic analysis of these cells' influence on circadian behavioral rhythms , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[15]  M. Menaker,et al.  A mutation of the circadian system in golden hamsters. , 1988, Science.

[16]  J. C. Hall,et al.  Spatial and temporal expression of the period gene in Drosophila melanogaster. , 1988, Genes & development.

[17]  M. Rosbash,et al.  Phase shifting of the circadian clock by induction of the Drosophila period protein. , 1994, Science.

[18]  M. W. Young,et al.  In situ localization of the per clock protein during development of Drosophila melanogaster , 1988, Molecular and cellular biology.

[19]  C. Helfrich-Förster.  The period clock gene is expressed in central nervous system neurons which also produce a neuropeptide that reveals the projections of circadian pacemaker cells within the brain of Drosophila melanogaster. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[20]  R. D. Lewis,et al.  Light-pulse phase response curves for the locomotor activity rhythm in Period mutants of Drosophila melanogaster , 1994 .

[21]  Jeffrey C. Hall,et al.  Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels , 1990, Nature.

[22]  A. Sehgal.  Genetic dissection of the circadian clock: A timeless story , 1995 .

[23]  P. Hardin.  Analysis of period mRNA cycling in Drosophila head and body tissues indicates that body oscillators behave differently from head oscillators , 1994, Molecular and cellular biology.

[24]  R J Konopka,et al.  Clock mutants of Drosophila melanogaster. , 1971, Proceedings of the National Academy of Sciences of the United States of America.

[25]  F. Jackson,et al.  Altered circadian pacemaker functions and cyclic AMP rhythms in the drosophila learning mutant dunce , 1994, Neuron.

[26]  A. Roca,et al.  Cloning of a structural and functional homolog of the circadian clock gene period from the giant silkmoth antheraea pernyi , 1994, Neuron.

[27]  A. Sehgal,et al.  Loss of circadian behavioral rhythms and per RNA oscillations in the Drosophila mutant timeless. , 1994, Science.

[28]  C S Pittendrigh,et al.  Temporal organization: reflections of a Darwinian clock-watcher. , 1993, Annual review of physiology.

[29]  A. Sehgal,et al.  Positional Cloning and Sequence Analysis of the Drosophila Clock Gene, timeless , 1995, Science.

[30]  Hongkui Zeng,et al.  Constitutive overexpression of the Drosophila period protein inhibits period mRNA cycling. , 1994, The EMBO journal.

[31]  Michael W. Young,et al.  Rhythmic Expression of timeless: A Basis for Promoting Circadian Cycles in period Gene Autoregulation , 1995, Science.

[32]  M. Rosbash,et al.  PER protein interactions and temperature compensation of a circadian clock in Drosophila , 1995, Science.

[33]  L. Vosshall,et al.  Block in nuclear localization of period protein by a second clock mutation, timeless. , 1994, Science.

[34]  S. Golden,et al.  Circadian clock mutants of cyanobacteria. , 1994, Science.

[35]  J. Dunlap,et al.  Negative feedback defining a circadian clock: autoregulation of the clock gene frequency. , 1994, Science.

[36]  L. Vosshall,et al.  Circadian rhythms in drosophila can be driven by period expression in a restricted group of central brain cells , 1995, Neuron.

[37]  M. Rosbash,et al.  Temporally regulated nuclear entry of the Drosophila period protein contributes to the circadian clock , 1995, Neuron.