FOR the first time, scientists have pieced together the 鈥減endulum鈥� of the
clock that maintains the daily rhythms of mammals. Their feat could help in the
search for drugs to treat sleeping disorders.
More is known about the mechanism of the fruit fly鈥檚 biological clock than
any other animal鈥檚. At the centre of the clock is a molecular pendulum made of
two proteins called PER (short for period) and TIM (timeless), whose
concentrations 鈥渟wing鈥� back and forth, in and out of the nucleus of the
cell.
First, the genes for PER and TIM are switched on, leading to a build-up of
the proteins outside the nucleus. When they reach a high enough concentration,
they link and enter the nucleus, where they start to disrupt their own
production. The level of the proteins then dwindles and this daily
cycle鈥攖he circadian rhythm鈥攕tarts again.
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Since mammalian versions of TIM and PER were identified, researchers
including Steven Reppert of Harvard Medical School in Boston have tried to
recreate the swing of the pendulum in mammalian cells in the lab. 鈥淲e thought we
had all the pieces,鈥� he says. 鈥淭he problem is we couldn鈥檛 get them to fit
迟辞驳别迟丑别谤.鈥�
Now they know why. It turns out that another protein, CRY (cryptochrome),
which fruit flies use only to synchronise the clock with light, is a crucial
piece of the mammalian pendulum. When Reppert and his colleagues added this
protein to mouse cells containing PER, both proteins entered the nucleus in more
than 90 per cent of the cells. CRY can also inhibit the production of PER (
Cell, vol 98, p 193). Unlike the insect protein, mammalian CRY doesn鈥檛 seem
to be affected by light.
Reppert says that now the components of the pendulum have been identified, it
might be possible to reset it using drugs. These could treat the disruptions of
circadian rhythm that come with jet lag and sleeping disorders.
鈥淚t鈥檚 an extremely interesting finding,鈥� says fly clock expert Michael Young
of Rockefeller University in New York. He speculates that the clock mechanism in
insects may be different from that in humans because light can reach nearly all
of a fly鈥檚 cells. But the mammalian clock evolved in a structure called the
suprachiasmatic nucleus deep in the brain. 鈥淢oving this clock into a constantly
dark tissue probably required a good deal of tinkering on nature鈥檚 part,鈥� says
Young.