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New measurements prove myosin
VI can act as molecular transporter
James E.
Kloeppel, Physical Sciences Editor
217-244-1073; kloeppel@uiuc.edu
2/2/06
 |
Click
photo to enlarge |
Photo
by L. Brian Stauffer |
| Paul
Selvin, a John Bardeen Faculty Scholar of Physics
at Illinois, has performed new measurements of one
molecular motor, myosin VI, that show it can function
individual ly as anchors or in pairs as transporters.
The new results have helped to resolve a research
controversy. |
|
|
CHAMPAIGN, Ill.
— In living organisms, hundreds of different kinds of molecular
motors perform a variety of essential, but little understood tasks that
result in such actions as muscle contraction, cell division and the
movement of materials within cells. Some motors act as transporters,
some serve as anchors, and some may do both.
New measurements performed at the University of Illinois at Urbana-Champaign
have shown that one of these molecular motors, myosin VI, can function
individually as anchors or in pairs as transporters. The new results
have helped to resolve a research controversy and better explain how
these little proteins perform their duties.
“Myosin VI is a tiny molecule that converts chemical energy into
mechanical motion and transports its load by ‘stepping’
along filaments of actin,” said Paul Selvin, a John Bardeen Faculty
Scholar of Physics at Illinois and a co-author of a paper to appear
in the Feb. 3 issue of the journal Molecular Cell. “Our measurements
prove that molecules of myosin VI can naturally form pairs and then
go for walks while carrying cargo.”
 |
Click
photo to enlarge |
Credit: Selvin
et al./Molecular Cell, Feb. 3, 2006. |
| Myosin
VI has been thought to be a monomer, but Park et al.
show that full-length myosin VI can be a dimer, and
can walk processively on actin. By increasing the
concentration (top to bottom in illustration), a greater
and greater fraction dimerizes in vitro, and walks
processively on actin. |
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|
In 2004, Selvin
and colleagues at Illinois and at the University of Pennsylvania reported
that myosin VI moved by a “hand-over-hand” mechanism in
steps of approximately 60 nanometers. (One nanometer is a billionth
of a meter, or about 10,000 times smaller than the width of a human
hair).
“In that experiment, we took two myosin VI monomers and ‘zippered’
their tops together to form a dimer – which then walked along
the actin,” Selvin said. “Some researchers thought that
by forcing the molecules to dimerize, our results were not representative
of what occurs naturally. Other researchers claimed that myosin VI was
always a monomer. We have now shown that these molecules can indeed
come together and dimerize on their own.”
In the latest experiment, the researchers repeated their earlier measurement,
but without zippering the monomers together. They used a high-precision
measurement technique developed at Illinois that can track the position
of a molecule to within 1.5 nanometers. The technique is called FIONA
(Fluorescence Imaging with One Nanometer Accuracy).
“We found that, at high enough concentrations, some of the myosin
molecules would find one another, they would dimerize, and they would
start walking,” Selvin said. “Those that did not dimerize
remained monomers and did not move. We also found that when the cargo-binding
domains were removed, the molecules dimerized more readily.
Selvin and his colleagues believe that myosin VI exists as a monomer
if not bound to cargo. Binding to cargo alters the conformation of the
molecule. At the same time, close proximity of two monomers bound to
cargo initiates dimerization.
“It is possible that different cargos bind to different regions
of the cargo-binding domain such that some cargos promote dimerization
and others do not, allowing the protein to function as either a dimer
(transporter) or a monomer (anchor), depending on its binding partners,”
the researchers wrote in the Molecular Cell paper.
“And,
while we have shown that myosin VI can be a transporter, we have not
shown that it is a transporter,” Selvin said. “To do that,
we have to look inside a living cell.”
Last year, Selvin’s team used FIONA to track the movements of
two other molecular motors, dynein and kinesin, inside living fruit
fly cells. “FIONA is capable of measuring the movement of myosin
VI within living cells,” Selvin said. “We are working on
that now.”
The co-authors
of the paper are Selvin, Illinois graduate student and lead author Hyokeun
Park; and Bhagavathi Ramamurthy, Mirko Travaglia, Dan Safer, Li-Qiong
Chen, Clara Franzini-Armstrong and H. Lee Sweeney at the University
of Pennsylvania.
The National Institutes of Health funded the work.
Editor’s note:
To reach Paul Selvin, call 217-417-6101; e-mail: selvin@uiuc.edu.
