Reference Report

Reference
Citation	Hara, T., Koh, K., Combs, D.J., Sehgal, A. (2011). Post-Translational Regulation and Nuclear Entry of TIMELESS and PERIOD Are Affected in New timeless Mutant. J. Neurosci. 31(27): 9982--9990. (Export to RIS)
FlyBase ID	FBrf0214253
Publication Type	Research paper
PubMed ID	21734289
PubMed Abstract	The molecular circadian clock consists of a feedback loop in which canonical clock proteins negatively regulate transcription of their own genes. Timed nuclear entry of these proteins is critical, but regulation of this event is poorly understood. In Drosophila melanogaster, the idea that nuclear entry of PERIOD (PER) is controlled by its partner protein TIMELESS (TIM) has been challenged by several studies. We identify here a novel mutation in the tim gene that eliminates behavioral rhythms while allowing robust expression of TIM and PER. Mutant TIM can bind to and stabilize PER. However, neither protein is expressed cyclically, and phosphorylation of both is reduced. In addition, TIM and PER are localized in the cytoplasm at all times of day, and mutant TIM attenuates transcriptional feedback by PER in cultured cells, suggesting that it holds PER in the cytoplasm. In fact, much of the reduced phosphorylation of PER in the new tim mutant appears to result from the cytoplasmic localization of PER. Interestingly, mutating a threonine near the original mutation produces similar phenotypes, raising the possibility that defective phosphorylation is the basis of TIM dysfunction in the novel tim mutant. We also show that a stable form of PER is cytoplasmic in tim-null flies. These studies establish an essential role of TIM in the timed nuclear entry of PER.
DOI	10.1523/JNEUROSCI.0993-11.2011
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Language of Publication	English
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Publication Type	Journal
Abbreviation	J. Neurosci.
Title	Journal of Neuroscience
Publication Year	1981-
ISBN/ISSN	0270-6474 1529-2401
Data from Reference
Alleles (8)
	per^{S47A.Scer\UAS} Scer\GAL4^elav-C155 Scer\GAL4^tim.PE tim⁰¹ tim^{PL.S.Scer\UAS.T:SV5\V5,T:Zzzz\His6} tim^PL tim^{S.Scer\UAS.T:SV5\V5,T:Zzzz\His6} tim^{TA.S.Scer\UAS.T:SV5\V5,T:Zzzz\His6}
Constructs (4)
	P{GAL4-tim.E} P{UAS-per.S47A} PBac{UAS-tim-V5-His.P115L} PBac{UAS-tim-V5-His}
Genes (8)
	cry jet Pdf per Scer\GAL4 T:SV5\V5 T:Zzzz\His6 tim
Insertions (1)
	P{GawB}elav^C155
Natural transposons (2)
	P-element Tni\piggyBac