Research shines spotlight on a key player in the dance of chromosomes

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Research shines spotlight on a key player in the dance of chromosomes

http://www.eurekalert.org/pub_releases/2008-05/uoia-rss051308.php

Cell division is essential to life, but the mechanism by which

emerging daughter cells organize and divvy up their genetic

endowments is little understood. In a new study, researchers at the

University of Illinois and Columbia University report on how a key

motor protein orchestrates chromosome movements at a critical stage

of cell division.

The study appeared in the Proceedings of the National Academy of

Sciences.

Within the complex world of the cell, motor proteins function as a

kind of postal service. These proteins carry cargo from one location

to another in the cell, a job that requires precision, in both the

location and the timing of delivery. They are fueled by a small

molecule, adenosine tri-phosphate (ATP).

Some motor proteins are essential to mitosis – the process by which

cell division occurs in higher organisms. During cell division it is

important for chromosomes to line up at the middle of the parent cell

allowing for their separation between the two daughter cells.

Motor proteins play a key role in the movement of chromosomes to and

from the poles of the cell. Should any of these processes lose

coordination, it could result in disease or cell death.

How chromosomes move during cell division is a question that is

fundamental to biology and is of importance in understanding many

diseases. University of Illinois physics professor Selvin and

his colleagues focused on a motor protein, centromeric protein E

(CENP-E) that is known to be associated with chromosomes.

" The question is whether CENP-E acts like a transporter or like an

anchor, " Selvin said.

" A transporter moves things around the cell, whereas an anchor sits

someplace in the cell, holds onto something, and causes the thing to

be held down, " Selvin said. " It turns out CENP-E is known to be an

anchor, but is it also a transporter? "

Earlier studies had established a role for CENP-E in aligning paired

chromosomes. This alignment is important for ensuring that one of

each pair makes its way into a different daughter cell.

CENP-E is part of a large class of proteins called kinesins. These

motor proteins walk across the cell on special tightropes, called

microtubules, using ATP as an energy source.

" The motion of 'normal` kinesin, kinesin-1, is now well known, "

Selvin said. " It turns out it's like a little person – it walks with

its two feet, one in front of the other. I was interested to know

whether the normal rules of how kinesin walks apply to these

different kinds of kinesins. "

" In vivo studies are hampered by the presence of lots of other

proteins, making it hard to study how much a single protein moves,

how fast it moves and how much force it produces, " said Hasan

Yardimci, a post doctoral researcher in Selvin's lab and lead author

on the study.

Instead, Yardimci used a technique that allowed him to look at one

molecule at a time.

The most direct way to measure how a protein moves is to watch it in

real time. Using special molecular bulbs called quantum dots, which

light up the protein, Yardimci was able to watch CENP-E move along

its microtubule tightrope. By resolving these motions on the

nanometer scale, he was able to make two key observations.

" The protein takes eight nanometer steps in a hand-over-hand

fashion, " Yardimci said. The protein moved in a direction consistent

with the way chromosomes move within cells, over lengths that are

normally observed during cell division.

To test the kind of loads that CENP-E could withstand, Yardimci set

up a tug of war between a micron-sized bead and the protein. As the

protein moved, it pulled on the bead.

By measuring the force on the bead, the researchers were able to

calculate how much force CENP-E could exert.

The observation that CENP-E shares several common features with

kinesin-1 provides insights into its molecular workings.

" We showed that it is likely that CENP-E moves chromosomes around, "

Selvin said. " That is, we showed that it is a transporter in vitro,

hauling around a little bead. Now we need to do it in vivo, on

chromosomes. "