Period Protein Research Articles

A model for circadian oscillations in the Drosophila period protein (PER)

The mechanism of circadian oscillations in the period protein (PER) in Drosophila is investigated by means of a theoretical model. Taking into account recent experimental observations, the model for the circadian clock is based on multiple phosphorylation of PER and on the negative feedback exerted by PER on the transcription of the period (per) gene. This minimal biochemical model provides a molecular basis for circadian oscillations of the limit cycle type. During oscillations, the peak in per mRNA precedes by several hours the peak in total PER protein. The results support the view that multiple PER phosphorylation introduces times delays which strengthen the capability of negative feedback to produce oscillations. The analysis shows that the rhythm only occurs in a range bounded by two critical values of the maximum rate of PER degradation. A similar result is obtained with respect to the rate of PER transport into the nucleus. The results suggest a tentative explanation for the altered period of per mutants, in terms of variations in the rate of PER degradation.

Temporally regulated nuclear entry of the Drosophila period protein contributes to the circadian clock.

The Drosophila period protein (PER) is a predominantly nuclear protein and a likely component of a circadian clock. PER is required for daily oscillations in the transcription of its own gene and thus participates in a circadian feedback loop. In this study, key pacemaker neurons of the Drosophila brain were examined to determine whether the subcellular distribution of PER changes with the time of day. Indeed, PER was found to accumulate in the cytoplasm for several hours before entering the nucleus during a narrow time window. Three long-period mutations (perL) cause a delay in the timing of nuclear translocation and a further delay at elevated temperature. The data indicate that regulation of PER nuclear entry is critical for circadian oscillations by providing a necessary temporal delay between PER synthesis and its effect on transcription.

Genetic dissection of the circadian clock: A timeless story

The period (per) gene is known to play a critical role in the generation and/or maintenance of circadian rhythms in Drosophila. Efforts to identify other molecular components of pacemaking pathways recently led to the isolation of a new clock mutation, timeless (tim). Circadian rhythms are eliminated in tim flies, probably due to the effect tim has on the subcellular localization of period protein (PER). Data indicate that the putative product(s) of the tim locus is essential for timekeeping in Drosophila. In this article I will review the isolation and phenotype of the tim mutation and also discuss its interaction with per.

The period clock gene is expressed in central nervous system neurons which also produce a neuropeptide that reveals the projections of circadian pacemaker cells within the brain of Drosophila melanogaster.

The period protein (PER) is a essential component of the circadian clock in Drosophila melanogaster. Although PER-containing pacemaker cells have been previously identified in the brain, the neuronal network that comprises the circadian clock remained unknown. Here it is shown that some PER neurons are also immunostained with an antiserum against the crustacean pigment-dispersing hormone (PDH). This antiserum reveals the entire arborization pattern of these pacemaker cells. The arborizations of these neurons are appropriate for modulation of the activity of many neurons and they might interact with PER-containing glial cells. A putative physiological role of PDH in the circadian system is discussed.

Block in Nuclear Localization of period Protein by a Second Clock Mutation, timeless

In wild-type Drosophila, the period protein (PER) is found in nuclei of the eyes and brain, and PER immunoreactivity oscillates with a circadian rhythm. The studies described here indicate that the nuclear localization of PER is blocked by timeless (tim), a second chromosome mutation that, like per null mutations, abolishes circadian rhythms. PER fusion proteins without a conserved domain (PAS) and some flanking sequences are nuclear in tim mutants. This suggests that a segment of PER inhibits nuclear localization in tim mutants. The tim gene may have a role in establishing rhythms of PER abundance and nuclear localization in wild-type flies.