Biology Reference
In-Depth Information
Next, we will take a more detailed look at circadian clocks in
Drosophila
,
and follow with an overview of the evidence that insect prothoracic glands
harbor their own peripheral clocks.
5. CIRCADIAN CORE CLOCK IN FLIES
Most organisms have evolved a circadian clock in order to anticipate
daily environmental changes in light, temperature, and mate availability.
Thus, they play pivotal roles in synchronizing and integrating physio-
logical and biochemical processes (
Allada & Chung, 2010
). Although circa-
dian rhythms are endogenous ("built-in,” self-sustained), they are adjusted
(entrained) by local environmental cues called zeitgebers (German for “syn-
chronizer”), such as daylight or temperature.
In order to be considered a circadian clock, a biological system needs to
have four fundamental characteristics: (1) an oscillatory event that occurs
approximately every 24 h; (2) these cycles occur even in constant conditions
(e.g. constant darkness), indicating the presence of a self-sustained clock; (3)
the rhythm must be entrainable by environmental cues, most commonly
daylight; and (4) the oscillatory rhythm is temperature-compensated, mean-
ing that shifts in the external temperature do not alter the periodicity of the
clock. Much of the work that contributes to our current understanding of
circadian clocks is derived from studies in
Drosophila
melanogaster (
Collins &
Blau,
2007; Dubruille & Emery, 2008; Stanewsky, 2003; Zheng & Sehgal,
2008
). The main components of the clock are transcription factors that act in
an auto-regulatory feedback loop (
Nitabach & Taghert, 2008
).
The heterodimer CLOCK/CYCLE binds to specific consensus
sequences (E-BOX) in the regulatory regions of their target genes. Among
these target genes are two circadian genes:
timeless
and
period
. Both
timeless
and
period
are actively transcribed during the day, but by early night, TIME-
LESS and PERIOD protein levels have risen in the cytoplasm, which allows
them to dimerize and translocate to the nucleus. There, TIMELESS/
PERIOD dimers bind to CLOCK/CYCLE, thereby blocking their
transcriptional activity. In the canonical core clock, CYCLE/CLOCK
heterodimers act as positive regulators of
period
and
timeless
transcription
(
Meyer, Saez, & Young, 2006; Yu, Zheng, Houl, Dauwalder, & Hardin,
2006
), which activates their own repressors, thus generating a transcrip-
tional feedback loop that builds the foundation of circadian periodicity
(
Kadener, Menet, Schoer, & Rosbash, 2008
)(
Fig. 1.2
). The molecular core
components CLOCK, CYCLE, TIMELESS, and PERIOD are modified at
the post-transcriptional
level allowing the system to fine-tune cycle
