Open Close
Reference
Citation
Li, Q., Li, Y., Wang, X., Qi, J., Jin, X., Tong, H., Zhou, Z., Zhang, Z.C., Han, J. (2017). Fbxl4 Serves as a Clock Output Molecule that Regulates Sleep through Promotion of Rhythmic Degradation of the GABAA Receptor.  Curr. Biol. 27(23): 3616--3625.e5.
FlyBase ID
FBrf0237417
Publication Type
Research paper
Abstract

The timing of sleep is tightly governed by the circadian clock, which contains a negative transcriptional feedback loop and synchronizes the physiology and behavior of most animals to daily environmental oscillations. However, how the circadian clock determines the timing of sleep is largely unclear. In vertebrates and invertebrates, the status of sleep and wakefulness is modulated by the electrical activity of pacemaker neurons that are circadian regulated and suppressed by inhibitory GABAergic inputs. Here, we showed that Drosophila GABAA receptors undergo rhythmic degradation in arousal-promoting large ventral lateral neurons (lLNvs) and their expression level in lLNvs displays a daily oscillation. We also demonstrated that the E3 ligase Fbxl4 promotes GABAA receptor ubiquitination and degradation and revealed that the transcription of fbxl4 in lLNvs is CLOCK dependent. Finally, we demonstrated that Fbxl4 regulates the timing of sleep through rhythmically reducing GABA sensitivity to modulate the excitability of lLNvs. Our study uncovered a critical molecular linkage between the circadian clock and the electrical activity of pacemaker neurons and demonstrated that CLOCK-dependent Fbxl4 expression rhythmically downregulates GABAA receptor level to increase the activity of pacemaker neurons and promote wakefulness.

PubMed ID
PubMed Central ID
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Curr. Biol.
    Title
    Current Biology
    Publication Year
    1991-
    ISBN/ISSN
    0960-9822
    Data From Reference
    Alleles (19)
    Genes (14)
    Physical Interactions (3)
    Cell Lines (1)
    Natural transposons (1)
    Insertions (3)
    Experimental Tools (1)
    Transgenic Constructs (6)