title: Light-dependent interaction between Drosophila CRY and the clock protein PER mediated by the carboxy terminus of CRY.
abstract: BACKGROUND
  The biological clock synchronizes the organism with the environment, responding to changes in light and temperature. Drosophila CRYPTOCHROME (CRY), a putative circadian photoreceptor, has previously been reported to interact with the clock protein TIMELESS (TIM) in a light-dependent manner. Although TIM dimerizes with PERIOD (PER), no association between CRY and PER has previously been revealed, and aspects of the light dependence of the TIM/CRY interaction are still unclear.
  
  
  RESULTS
  Behavioral analysis of double mutants of per and cry suggested a genetic interaction between the two loci. To investigate whether this was reflected in a physical interaction, we employed a yeast-two-hybrid system that revealed a dimerization between PER and CRY. This was further supported by a coimmunoprecipitation assay in tissue culture cells. We also show that the light-dependent nuclear interactions of PER and TIM with CRY require the C terminus of CRY and may involve a trans-acting repressor.
  
  
  CONCLUSIONS
  This study shows that, as in mammals, Drosophila CRY interacts with PER, and, as in plants, the C terminus of CRY is involved in mediating light responses. A model for the light dependence of CRY is discussed.
authors.affiliation: Department of Biology, University of Leicester, University Road, LE1 7RH, Leicester, United Kingdom. er6@le.ac.uk
authors.forename: E
authors.initials: E
authors.lastname: Rosato
authors.forename: V
authors.initials: V
authors.lastname: Codd
authors.forename: G
authors.initials: G
authors.lastname: Mazzotta
authors.forename: A
authors.initials: A
authors.lastname: Piccin
authors.forename: M
authors.initials: M
authors.lastname: Zordan
authors.forename: R
authors.initials: R
authors.lastname: Costa
authors.forename: C P
authors.initials: CP
authors.lastname: Kyriacou
mesh_terms: D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D002460:Cell Line; D002940:Circadian Rhythm / Q000502:physiology*; D056931:Cryptochromes; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology*; D005136:Eye Proteins; D005420:Flavoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015151:Immunoblotting; D019476:Insect Proteins / Q000378:metabolism; D008027:Light; D008124:Locomotion / Q000235:genetics / Q000502:physiology; D008954:Models, Biological; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D056950:Period Circadian Proteins; D017956:Photoreceptor Cells, Invertebrate; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013696:Temperature; D020798:Two-Hybrid System Techniques
chemical_list: D056931:Cryptochromes; D029721:Drosophila Proteins; D005136:Eye Proteins; D005420:Flavoproteins; D019476:Insect Proteins; D009687:Nuclear Proteins; C539040:PER protein, Drosophila; D056950:Period Circadian Proteins; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins; C119828:cry protein, Drosophila; C096445:tim protein, Drosophila