Requirement of mammalian Timeless for circadian rhythmicity.
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.
Barnes
Jessica W
JW
Department of Cell and Structural Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Tischkau
Shelley A
SA
Barnes
Jeffrey A
JA
Mitchell
Jennifer W
JW
Burgoon
Penny W
PW
Hickok
Jason R
JR
Gillette
Martha U
MU
D000818:Animals; D001683:Biological Clocks; D018797:Cell Cycle Proteins; D002460:Cell Line; D002940:Circadian Rhythm; D056931:Cryptochromes; D029721:Drosophila Proteins; D004594:Electrophysiology; D005136:Eye Proteins; D005420:Flavoproteins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D009474:Neurons / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D056950:Period Circadian Proteins; D017956:Photoreceptor Cells, Invertebrate; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D043562:Receptors, G-Protein-Coupled; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013493:Suprachiasmatic Nucleus / Q000502:physiology*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D018797:Cell Cycle Proteins; D056931:Cryptochromes; D029721:Drosophila Proteins; D005136:Eye Proteins; D005420:Flavoproteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; C539022:PER1 protein, human; C421902:PER2 protein, human; C512644:PER3 protein, human; C539023:Per1 protein, mouse; C539024:Per1 protein, rat; C513312:Per2 protein, mouse; C513311:Per2 protein, rat; C512645:Per3 protein, mouse; C512646:Per3 protein, rat; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; C509769:TIMELESS protein, human; C509770:Timeless protein, mouse; D014157:Transcription Factors; C119828:cry protein, Drosophila