Study uncovers distinct
work habits of molecular motors
BY KRISTIN WEIDENBACH
Stanford researchers have
found that the tiny molecular motors that move our arms
and legs and keep our hearts pumping work differently
when they are ferrying cargo around inside our cells.
Using methods that allow them to look at individual
motors, the researchers have found that the motors in
nerve cells carry molecules great distances by
progressing slowly and steadily whereas those in muscle
cells generate instant speed and force by working rapidly
and cooperatively.
The miniature biological
motors, known as myosins, latch on to specialized tracks
running throughout our cells and cause our bodies to
move. Millions of myosins in our skeletal muscles allow
our arm to bend and flex to reach out and pick up a cup.
Related myosins in the cardiac muscle keep our heart
beating regularly and those in our smooth muscle keep
food moving rhythmically through our intestines. The
myosins in our nerve cells carry packages of nutrients
and supplies wherever they may be needed to support a
growing nerve tip or replenish lost materials. These
myosins must be capable of covering great distances, such
as the length of the sciatic nerve, which stretches from
hip to toe.
"All movement in
cells and all movement people undergo, requires these
molecular motors," said James Spudich, PhD, Douglass
M. and Nola Leishman Professor of Biochemistry.
Spudich and his colleagues
have found that myosin-V, the kind of myosin found in
nerve cells, moves processively, meaning that the motors
attach to their track and don't release until reaching
their destination. These are the first myosins found to
move in this way but another class of molecular motors,
known as kinesins, moves in the same manner. Myosins
found in muscle cells, on the other hand, are continually
hopping on and off of their track. Because they are
moving more quickly and generating more force in order to
collectively move a muscle, they burn energy much faster
and must often detach from the track to replenish
themselves.
"It is the first
description of a myosin family member that moves in a way
that people have reserved in their thinking for kinesin
motors," said Spudich. Members of Spudich's lab,
graduate student Amit Mehta, and postdoctoral fellows
Ronald Rock, PhD, and Matthias Rief, PhD, agree that some
scientists will have to set aside their long-held beliefs
about how molecular motors move, based on the team's
work, which was published in the August 5 issue of Nature.
Some scientists would have
predicted from biochemical studies that the myosin motors
in the brain and nerve cells move in a way more
characteristic of kinesin motors, but until individual
motors could be seen in action, researchers were left
wondering, said Spudich. "If you can see at a single
molecule level, then suddenly you take all the mystery
out of it," he said. The finding was made possible
by techniques developed at Stanford and Princeton
University that allow researchers to watch single motors
in action. They can even measure how far the tiny motors
move and how hard they can tug on their actin tracks.
Researchers in the Spudich
lab first turned their attention to myosin-V because it
was found to be the site of a mutation that causes a skin
and neurological disease called Griscelli syndrome.
Spudich believes that many other diseases will also be
found to be linked to aberrant molecular motors.
Researchers at Yale
University and the University of North Carolina at Chapel
Hill collaborated on the study, which was funded by the
National Institutes of Health. SR
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