Requirement of Mammalian Timeless for Circadian Rhythmicity
- 17 October 2003
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 302 (5644) , 439-442
- https://doi.org/10.1126/science.1086593
Abstract
Despite a central circadian role in Drosophila for the transcriptional regulator Timeless (dTim), the relevance of mammalian Timeless (mTim) remains equivocal. Conditional knockdown of mTim protein expression in the rat suprachiasmatic nucleus (SCN) disrupted SCN neuronal activity rhythms, and altered levels of known core clock elements. Full-length mTim protein (mTIM-fl) exhibited a 24-hour oscillation, where as a truncated isoform (mTIM-s) was constitutively expressed. mTIM-fl associated with the mammalian clock Period proteins (mPERs) in oscillating SCN cells. These data suggest that mTim is required for rhythmicity and is a functional homolog of dTim on the negative-feedback arm of the mammalian molecular clockwork.Keywords
This publication has 25 references indexed in Scilit:
- Ca2+/cAMP Response Element-binding Protein (CREB)-dependent Activation of Per1 Is Required for Light-induced Signaling in the Suprachiasmatic Nucleus Circadian ClockJournal of Biological Chemistry, 2003
- Antagonism of vasoactive intestinal peptide mRNA in the suprachiasmatic nucleus disrupts the rhythm of FRAs expression in neuroendocrine dopaminergic neuronsJournal of Comparative Neurology, 2002
- Additive effect of mPer1 and mPer2 antisense oligonucleotides on light-induced phase shiftNeuroReport, 2001
- Molecular Characterization and Nuclear Localization of Rat timeless-like Gene ProductBiochemical and Biophysical Research Communications, 2000
- Molecular Genetics of Circadian Rhythms in MammalsAnnual Review of Neuroscience, 2000
- Light-Independent Role of CRY1 and CRY2 in the Mammalian Circadian ClockScience, 1999
- Immortal Time: Circadian Clock Properties of Rat Suprachiasmatic Cell LinesScience, 1999
- Mammalian Circadian Autoregulatory LoopNeuron, 1998
- In vivo antisense antagonism of vasoactive intestinal peptide in the suprachiasmatic nuclei causes aging-like changes in the estradiol- induced luteinizing hormone and prolactin surgesEndocrinology, 1996
- Loss of Circadian Behavioral Rhythms and per RNA Oscillations in the Drosophila Mutant timelessScience, 1994