Molecular Motors and Brakes Work Together in Cells
Interaction sheds light on how cell's inner "skeleton" is organized
– Researchers at the University
of Pennsylvania School of Medicine have discovered
– components responsible for shape, movement, and replication
within cells – use proteins
that act as molecular motors and brakes to organize into their correct
structure. If microtubules are not formed properly such basic functions
division and transport can go wrong, which may have implications
in such disease processes as cancer
The study, published in the January issue of Cell,
is featured on the cover of that issue.
Microtubules are structures that help give shape to many types of
cells, form the spindle
(view video below) – a structure
important in cell division – and act as a railroad, of sorts,
upon which molecular motors move protein packages for waste removal
Microtubules in live fission
Top: Yeast microtubules come together to form the spindle,
the cellular component that pulls duplicated chromosomes apart
into their respective daughter cells during cell division.
After about 30 minutes of cell division the microtubules of
the spindle disperse.
Bottom: Dispersed microtubules during interphase of the cell
cycle, in which the cell is "resting."
Video Courtesy: Phong Tran, PhD, University
of Pennsylvania School of Medicine
In the Cell study, the investigators, working with fissionyeast
cells, showed that stable end-to-end arrays of microtubules can
be achieved by a balance between the sliding by a molecular motor
called klp2p and the braking of a microtubule-associated protein
(MAP) called ase1p. Specifically, they showed that a preexisting
“mother” microtubule acts as a platform on which a new
microtubule can be formed (view video below).
The new “daughter” microtubule grows and moves along
the mother microtubule. In time, the daughter grows beyond the end
of the mother to ultimately produce two microtubules, connected
by the cross-linking MAP ase1p.
Daughter microtubule (red) being
formed on mother microtubule (red), within yeast cell (dashed
line). Green represents the molecular motors, the kinesin
proteins klp2, of each microtubule.
Video Courtesy: Phong Tran, PhD, University of Pennsylvania
School of Medicine
“Imagine that the daughter microtubule is a short train on
the track of the mother microtubule,” explains Tran. “The
molecular motor is the train’s engine, but the problem is
that the cargo – the molecular brakes – gets longer,
slowing down the daughter train. But when the train gets to the
end of the track it remains attached to the end of mother microtubule.
At the tail end, it stops moving and that defines the region of
overlap. Our work shows that the cell can make microtubule structures
of defined lengths stable by coordinating the sliding of the motors
and the slowing of the brakes.”
If microtubule-based structures are not formed properly because
of failures in brakes or motors, such basic functions as cell division
and cell transport can go awry, with such diseases as cancer and
dementia possibly resulting. “For the first time we have shown
how MAPs and motors work together in a mechanistic way,” says
Tran. “This is important and it will make other people who
study microtubules rethink how they study the cell.”
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