CELLS bustle like a city. They make DNA, pack it into chromosomes, truck in
nutrients and cart out wastes. This work is done by thousands of tiny motors.
鈥淚f a cell didn鈥檛 have any molecular motors, it wouldn鈥檛 be alive,鈥� says James
Spudich, a biochemist at Stanford University.
Spudich and his team have set their sights on finding out how these
micromachines are controlled. The payoff could be better treatments for
disease.
Perhaps the body鈥檚 best-known motor makes muscle contract. Muscle contains
two slender proteins, myosin and actin. A molecule of myosin ratchets along an
actin fibre with a motion that resembles a finger gesturing 鈥渃ome hither鈥�. A few
years ago, Spudich and his colleagues measured the force exerted by this
interaction. They stretched an actin filament between two plastic beads and let
a myosin molecule grab it. The myosin tugged with a force of several
piconewtons鈥攁bout a tenth the force exerted by a handheld laser pointer
hitting a screen.
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Several other motors have now been tested. The first was kinesin, which
transports packages of protein around inside the cell on rails called
microtubules. Spudich鈥檚 colleague Steve Block and his team found that this motor
packs a hefty 6 piconewtons. Now Spudich鈥檚 group has characterised a myosin from
brain tissue called myosin five (myosin V). Its job is to transport cargo along
actin filaments in nerve endings.
Myosin V illustrates how little is known about motor control. Kinesin handles
most of the transport from a neuron鈥檚 bloated cell body鈥攚here proteins are
made鈥攐ut along its axons and dendrites. It travels the microtubule
highways, and at the far end it hands over to myosin V, which delivers along
small roads made of actin. Each parcel has both kinesin and myosin V bound to
it, but uses only one at a time. 鈥淚t has to know when to shut one motor off and
switch tracks,鈥� says Spudich. How this happens is still a mystery.
The cell is like a huge city road network, says Spudich, yet we know
virtually nothing about the traffic signals. Even more of a mystery is the way a
cell can change the layout of its entire city. For example, when a cell begins
to divide, it may change shape and tear down unnecessary microtubules.
Understanding more about motor control could lead to better cancer drugs.
Taxol, originally extracted from the bark of the Pacific yew, works by
preventing the breakdown of microtubules, which interferes with the 鈥渃ity
conversion鈥� needed for cells to divide. Spudich says a more effective anticancer
strategy鈥攚ith fewer side effects鈥攎ight be to target specific motors,
rather than the microtubule tracks that so many motors share. 鈥淭here is a wealth
of targets that is virtually unexplored,鈥� he says.