Featured Research

from universities, journals, and other organizations

How microtubules let go of their attachments during cell division

Date:
May 14, 2010
Source:
Whitehead Institute for Biomedical Research
Summary:
Researchers have determined how cells regulate the chromosome/microtubule interface, which is central to proper chromosomal distribution during cell division. The chromosome/microtubule interface is critical during cell division. If a microtubule attaches incorrectly to a chromosome and cell division proceeds, the chromosomes may divide unevenly, resulting in cells with an incorrect number of chromosomes. Aberrant distribution of chromosomes can lead to cancer or premature cell death.

Whitehead Institute researchers have determined a key part of how cells regulate the chromosome/microtubule interface, which is central to proper chromosomal distribution during cell division.

Related Articles


"This is the surveillance machinery that makes sure that the chromosomes are divided correctly between cells," says Whitehead Member Iain Cheeseman.

The findings are published in the journal Molecular Cell.

During cell division, the cell's DNA is consolidated into X-shaped chromosome pairs that align along the middle of the cell. Where the arms of the X cross, each chromosome has two kinetochores--protein complexes that facilitate microtubule attachment to the chromosome. As cell division progresses, these microtubules pull the right or left half of each chromosome towards the spindle poles to separate them to opposite ends of the cell.

Problems can frequently arise during this process. As a microtubule extends from a spindle pole, it may attach incorrectly to a kinetochore. When this happens, the cell needs a way to detect the mistake, detach the problematic microtubule, and reattach it correctly. If the issue is not addressed and cell division proceeds, the chromosomes typically fail to divide evenly, resulting in cells with the wrong number of chromosomes. This aberrant distribution of chromosomes can lead to cancer or premature cell death.

To correct attachment problems, cells rely on a system of phosphorylation -- the addition of a phosphate group to certain proteins -- to control whether or not microtubules stay bound to the kinetochore.

According to the Molecular Cell paper, the enzyme Aurora B resides within the inner kinetochore and adds phosphates to a key player in the kinetochore, called the KMN network, that attaches to the microtubule.

Aurora B's ability to phosphorylate a molecule wanes the farther that molecule is from the enzyme. In the case of a microtubule properly attached to the kinetochore, the microtubule's increased tension on the KMN network pulls the network taut and farther away from Aurora B, thereby reducing Aurora B's ability to phosphorylate the KMN network. If the microtubule is not correctly attached, the KMN network is not pulled away from Aurora B. The decreased distance lets Aurora B keep the KMN network phosphorylated, which destabilizes the microtubule's attachment to the kinetochore and allows the microtubule to detach and try again.

The KMN network is composed of several subunits arranged at different distances from Aurora B. Each subunit can be individually phosphorylated by Aurora B, which allows the attachment/detachment system to be controlled much like a dimmer rather than an on-off switch.

"This is a very sensitive system that allows the cell to dynamically respond to different attachment problems," says Julie Welburn, first author of the Molecular Cell paper and a postdoctoral researcher in the Cheeseman lab.

But for this system to function properly, phosphates also need to be removed from the KMN network to allow new microtubule attachments to form. In a recent Journal of Cell Biology article, the Cheeseman lab collaborated with researchers at the University of Pennsylvania to show that another enzyme, protein phosphatase 1 (PP1), counteracts Aurora B's activity. As tension increases at a properly attached microtubule, one KMN network subunit recruits PP1. PP1 then removes the phosphates from the molecules phosphorylated by Aurora B, thereby stabilizing the microtubule's attachment to the kinetochore. However, the recruitment of PP1 itself to kinetochores is controlled by Aurora B activity.

"I think it's really cool that this process is not a simple tug of war between adding a phosphate and taking it away," says Cheeseman, who is also an associate professor of biology at MIT. "But that PP1 itself is sensitive to the overall level of Aurora B activity. So, the higher the Aurora B activity, the lower the PP1 activity, and vice versa. It sets up this balance between them, so that you can switch between high phosphorylation and no phosphorylation very quickly."

Although the two papers clarify certain aspects of the microtubule interface, the picture is not yet complete.

"We're slowly finding the other targets in this process and understanding even better how this mechanism works to correct microtubule attachments," says Welburn.

This research was supported by the Smith Family Foundation, the Massachusetts Life Sciences Center, the Searle Scholars Program, and the National Institute Of General Medical Sciences.

Iain Cheeseman's primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also an assistant professor of biology at Massachusetts Institute of Technology.


Story Source:

The above story is based on materials provided by Whitehead Institute for Biomedical Research. The original article was written by Nicole Giese. Note: Materials may be edited for content and length.


Journal References:

  1. Julie P.I. Welburn, Mathijs Vleugel, Dan Liu, John R. Yates, Michael A. Lampson, Tatsuo Fukagawa, Iain M. Cheeseman. Aurora B phosphorylates spatially distinct targets to differentially regulate the kinetochoremicrotubule interface. Molecular Cell, 2010; 38 (3): 383-392 DOI: 10.1016/j.molcel.2010.02.034
  2. D. Liu, M. Vleugel, C. B. Backer, T. Hori, T. Fukagawa, I. M. Cheeseman, M. A. Lampson. Regulated targeting of protein phosphatase 1 to the outer kinetochore by KNL1 opposes Aurora B kinase. The Journal of Cell Biology, 2010; 188 (6): 809 DOI: 10.1083/jcb.201001006

Cite This Page:

Whitehead Institute for Biomedical Research. "How microtubules let go of their attachments during cell division." ScienceDaily. ScienceDaily, 14 May 2010. <www.sciencedaily.com/releases/2010/05/100513123722.htm>.
Whitehead Institute for Biomedical Research. (2010, May 14). How microtubules let go of their attachments during cell division. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2010/05/100513123722.htm
Whitehead Institute for Biomedical Research. "How microtubules let go of their attachments during cell division." ScienceDaily. www.sciencedaily.com/releases/2010/05/100513123722.htm (accessed October 25, 2014).

Share This



More Plants & Animals News

Saturday, October 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deep Sea 'mushroom' Could Be Early Branch on Tree of Life

Deep Sea 'mushroom' Could Be Early Branch on Tree of Life

Reuters - Innovations Video Online (Oct. 24, 2014) Miniature deep sea animals discovered off the Australian coast almost three decades ago are puzzling scientists, who say the organisms have proved impossible to categorise. Academics at the Natural History of Denmark have appealed to the world scientific community for help, saying that further information on Dendrogramma enigmatica and Dendrogramma discoides could answer key evolutionary questions. Jim Drury has more. Video provided by Reuters
Powered by NewsLook.com
Black Bear Cub Goes Sunday Shopping

Black Bear Cub Goes Sunday Shopping

Reuters - Light News Video Online (Oct. 23, 2014) Price check on honey? Bear cub startles Oregon drugstore shoppers. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com
Dances With Wolves in China's Wild West

Dances With Wolves in China's Wild West

AFP (Oct. 23, 2014) One man is on a mission to boost the population of wolves in China's violence-wracked far west. The animal - symbol of the Uighur minority there - is under threat with a massive human resettlement program in the region. Duration: 00:41 Video provided by AFP
Powered by NewsLook.com
Breakfast Debate: To Eat Or Not To Eat?

Breakfast Debate: To Eat Or Not To Eat?

Newsy (Oct. 23, 2014) Conflicting studies published in the same week re-ignited the debate over whether we should be eating breakfast. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Plants & Animals

Earth & Climate

Fossils & Ruins

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins