title: QUASIMODO, a Novel GPI-anchored zona pellucida protein involved in light input to the Drosophila circadian clock.
abstract: BACKGROUND
  Circadian clocks are synchronized to the solar day via visual and specialized photoreceptors. In Drosophila, CRYPTOCHROME (CRY) is a major photoreceptor that mediates resetting of the circadian clock via light-dependent degradation of the clock protein TIMELESS (TIM). However, in the absence of CRY, this TIM-mediated resetting still occurs in some pacemaker neurons, resulting in synchronized behavioral rhythms when flies are exposed to light-dark cycles. Even in the additional absence of visual photoreception, partial molecular and behavioral light synchronization persists. Therefore, other important clock-related photoreceptive and synchronization mechanisms must exist.
  
  
  RESULTS
  We identified a novel clock-controlled gene (quasimodo) that encodes a light-responsive and membrane-anchored Zona Pellucida domain protein that supports light-dependent TIM degradation. Whereas wild-type flies become arrhythmic in constant light (LL), quasimodo mutants elicit rhythmic expression of clock proteins and behavior in LL. QUASIMODO (QSM) can function independently of CRY and is predominantly expressed within CRY-negative clock neurons. Interestingly, downregulation of qsm in the clock circuit restores LL clock protein rhythms in qsm-negative neurons, indicating that qsm-mediated light input is not entirely cell autonomous and can be accessed by the clock circuit.
  
  
  CONCLUSIONS
  Our findings indicate that QSM constitutes part of a novel and CRY-independent light input to the circadian clock. Like CRY, this pathway targets the clock protein TIM. QSM's light-responsive character in conjunction with the predicted localization at the outer neuronal membrane suggests that its function is linked to a yet unidentified membrane-bound photoreceptor.
authors.affiliation: School of Biological and Chemical Sciences, Queen Mary, University of London, London E1 4NS, UK.
authors.forename: Ko Fan
authors.initials: KF
authors.lastname: Chen
authors.forename: Nicolai
authors.initials: N
authors.lastname: Peschel
authors.forename: Radka
authors.initials: R
authors.lastname: Zavodska
authors.forename: Hana
authors.initials: H
authors.lastname: Sehadova
authors.forename: Ralf
authors.initials: R
authors.lastname: Stanewsky
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D057906:Circadian Clocks / Q000502:physiology*; D003001:Cloning, Molecular; D017931:DNA Primers; D004330:Drosophila / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D007150:Immunohistochemistry; D055537:Light Signal Transduction / Q000235:genetics / Q000502:physiology*; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000378:metabolism; D017440:Photoperiod; D016133:Polymerase Chain Reaction; D034622:RNA Interference; D015044:Zona Pellucida / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D029721:Drosophila Proteins; D058851:GPI-Linked Proteins; C560826:QSM protein, Drosophila; C096445:tim protein, Drosophila