Abstract
Robust circadian oscillations of the proteins PERIOD (PER) and TIMELESS (TIM) are hallmarks of a functional clock in the fruit fly Drosophila melanogaster. Early morning phosphorylation of PER by the kinase Doubletime (DBT) and subsequent PER turnover is an essential step in the functioning of the Drosophila circadian clock. Here using time-lapse fluorescence microscopy we study PER stability in the presence of DBT and its short, long, arrhythmic, and inactive mutants in S2 cells. We observe robust PER degradation in a DBT allele-specific manner. With the exception of doubletime-short (DBT S), all mutants produce differential PER degradation profiles that show direct correspondence with their respective Drosophila behavioral phenotypes. The kinetics of PER degradation with DBT S in cell culture resembles that with wild-type DBT and posits that, in flies DBT S likely does not modulate the clock by simply affecting PER degradation kinetics. For all the other tested DBT alleles, the study provides a simple model in which the changes in Drosophila behavioral rhythms can be explained solely by changes in the rate of PER degradation.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 27654-27662 |
| Number of pages | 9 |
| Journal | Journal of Biological Chemistry |
| Volume | 286 |
| Issue number | 31 |
| DOIs | |
| State | Published - Aug 5 2011 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Molecular Biology
Cite this
Kinetics of doubletime kinase-dependent degradation of the Drosophila period protein. / Syed, Sheyum; Saez, Lino; Young, Michael W.
In: Journal of Biological Chemistry, Vol. 286, No. 31, 05.08.2011, p. 27654-27662.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Kinetics of doubletime kinase-dependent degradation of the Drosophila period protein
AU - Syed, Sheyum
AU - Saez, Lino
AU - Young, Michael W.
PY - 2011/8/5
Y1 - 2011/8/5
N2 - Robust circadian oscillations of the proteins PERIOD (PER) and TIMELESS (TIM) are hallmarks of a functional clock in the fruit fly Drosophila melanogaster. Early morning phosphorylation of PER by the kinase Doubletime (DBT) and subsequent PER turnover is an essential step in the functioning of the Drosophila circadian clock. Here using time-lapse fluorescence microscopy we study PER stability in the presence of DBT and its short, long, arrhythmic, and inactive mutants in S2 cells. We observe robust PER degradation in a DBT allele-specific manner. With the exception of doubletime-short (DBT S), all mutants produce differential PER degradation profiles that show direct correspondence with their respective Drosophila behavioral phenotypes. The kinetics of PER degradation with DBT S in cell culture resembles that with wild-type DBT and posits that, in flies DBT S likely does not modulate the clock by simply affecting PER degradation kinetics. For all the other tested DBT alleles, the study provides a simple model in which the changes in Drosophila behavioral rhythms can be explained solely by changes in the rate of PER degradation.
AB - Robust circadian oscillations of the proteins PERIOD (PER) and TIMELESS (TIM) are hallmarks of a functional clock in the fruit fly Drosophila melanogaster. Early morning phosphorylation of PER by the kinase Doubletime (DBT) and subsequent PER turnover is an essential step in the functioning of the Drosophila circadian clock. Here using time-lapse fluorescence microscopy we study PER stability in the presence of DBT and its short, long, arrhythmic, and inactive mutants in S2 cells. We observe robust PER degradation in a DBT allele-specific manner. With the exception of doubletime-short (DBT S), all mutants produce differential PER degradation profiles that show direct correspondence with their respective Drosophila behavioral phenotypes. The kinetics of PER degradation with DBT S in cell culture resembles that with wild-type DBT and posits that, in flies DBT S likely does not modulate the clock by simply affecting PER degradation kinetics. For all the other tested DBT alleles, the study provides a simple model in which the changes in Drosophila behavioral rhythms can be explained solely by changes in the rate of PER degradation.
UR - http://www.scopus.com/inward/record.url?scp=79961004102&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79961004102&partnerID=8YFLogxK
U2 - 10.1074/jbc.M111.243618
DO - 10.1074/jbc.M111.243618
M3 - Article
C2 - 21659538
AN - SCOPUS:79961004102
VL - 286
SP - 27654
EP - 27662
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 31
ER -