Featured Research

from universities, journals, and other organizations

A mitosis mystery solved: How chromosomes align perfectly in a dividing cell

Date:
February 12, 2012
Source:
Whitehead Institute for Biomedical Research
Summary:
Although the process of mitotic cell division has been studied intensely for more than 50 years, researchers have only now solved the mystery of how cells correctly align their chromosomes during symmetric mitosis.

Rendering of mitosis. The process of mitosis is extremely precise; when it comes to manipulating DNA, cells verge on being obsessive and with good reason. Gaining or losing a chromosome during cell division can lead to cell death, developmental disorders, or cancer.
Credit: © nobeastsofierce / Fotolia

To solve a mystery, sometimes a great detective need only study the clues in front of him. Like Agatha Christie's Hercule Poirot and Arthur Conan Doyle's Sherlock Holmes, Tomomi Kiyomitsu used his keen powers of observation to solve a puzzle that had mystified researchers for years: in a cell undergoing mitotic cell division, what internal signals cause its chromosomes to align on a center axis?

"People have been looking at these proteins and players in mitosis for decades, and no one ever saw what Tomomi observed," says Whitehead Institute Member Iain Cheeseman. "And it's very clear that these things are happening. These are very strong regulatory paradigms that are setting down these cell division axes. And careful cell biology allowed him to see that this was occurring. People have been looking at this for a long time, but never with the careful eyes he brought to it."

Kiyomitsu, a postdoctoral researcher in Cheeseman's lab, published his work in a recent issue of the journal Nature Cell Biology.

The process of mitotic cell division has been studied intensely for more than 50 years. Using fluorescence microscopy, today's scientists can see the tug-of-war cells undergo as they move through mitosis. Thread-like proteins, called microtubules, extend from one of two spindle poles on either side of the cell and attempt to latch onto the duplicated chromosomes. This entire "spindle" structure acts to physically distribute the chromosomes, but it is not free floating in the cell. In addition to microtubules from both spindle poles that attach to all of the chromosomes, astral microtubules that are connected to the cell cortex -- a protein layer lining the cell membrane -- act to pull the spindle poles back and forth within the cell until the spindle and chromosomes align down the center axis of the cell. Then the microtubules tear the duplicated chromosomes in half, so that ultimately one copy of each chromosome ends up in each of the new daughter cells.

The process of mitosis is extremely precise; when it comes to manipulating DNA, cells verge on being obsessive and with good reason. Gaining or losing a chromosome during cell division can lead to cell death, developmental disorders, or cancer.

As Kiyomitsu watched mitosis unfold in symmetrically dividing human cells, he noticed that when the spindle oscillates toward the cell's center, a partial halo of the protein dynein lines the cell cortex on the side farther away from the spindle. As the spindle swings to the left, dynein appears on the right, but when the spindle swing to the right, dynein vanishes and reappears on the left side.

For Kiyomitsu, the key to the alignment mystery was dynein, which is known as a motor protein that "walks" molecular cargoes along microtubules. Kiyomitsu determined that in this case, dynein is anchored to the cell cortex by a complex that includes the protein LGN, short for leucine-glycine-asparagine-enriched protein. Instead of moving along an astral microtubule, the stationary dynein acts as a winch to pull on the spindle pole, and the microtubules and chromosomes attached to it, toward the cell cortex.

Kiyomitsu found that when a spindle pole comes within close proximity to the cell cortex, a signal from a protein called Polo-like kinase 1 (Plk1) emanates from the spindle pole, knocking dynein off of LGN and the cell cortex, stopping the spindle pole's forward motion, and freeing dynein to move to the opposite side of the cell. These oscillations continue with decreasing amplitude until the spindle settles along the cell's center axis.

As he was deciphering dynein's role in spindle alignment, Kiyomitsu noticed that a layer of LGN extends all around the cell cortex, except in the areas that are closest to the chromosomes. As the chromosomes swing back and forth, the area cleared of LGN changes in response. Because dynein needs to anchor to LGN, this cleared area ensures that dynein can only attach and pull to the right and left of the aligning chromosomes, rather than from above and below.

After testing a couple of signaling molecules associated with chromosomes, Kiyomitsu determined that a signal from the chromosomes, involving the ras-related nuclear protein (Ran), blocks LGN, and therefore dynein, from attaching to the cell cortex closest to the chromosomes. Ran bound to guanosine-5'-triphosphate (Ran-GTP), which controls nuclear import in the interphase stage of mitosis, had previously been suggested to control spindle assembly during mitosis in germ cells, but roles for the Ran gradient in mitotic non-germ cells were unclear. Kiyomitsu's work suggests a key role for Ran in directing spindle orientation.

Kiyomitsu says the axis that the spindle poles travel along is crucial to cells.

"The spindle orientation is critical for maintaining the balance between stem cells and mature cells during development," he notes. "And if this orientation becomes dysregulated or misregulated, it is reported that this may contribute to causing cancer even if chromosomes are properly segregated."

This work was supported by the Massachusetts Life Sciences Center, the Searle Scholars Program, and the Human Frontiers Science Foundation, the National Institutes of Health (NIH)/National Institute of General Medical Sciences, and the American Cancer Society.


Story Source:

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


Journal Reference:

  1. Tomomi Kiyomitsu, Iain M. Cheeseman. Chromosome- and spindle-pole-derived signals generate an intrinsic code for spindle position and orientation. Nature Cell Biology, 2012; DOI: 10.1038/ncb2440

Cite This Page:

Whitehead Institute for Biomedical Research. "A mitosis mystery solved: How chromosomes align perfectly in a dividing cell." ScienceDaily. ScienceDaily, 12 February 2012. <www.sciencedaily.com/releases/2012/02/120212192552.htm>.
Whitehead Institute for Biomedical Research. (2012, February 12). A mitosis mystery solved: How chromosomes align perfectly in a dividing cell. ScienceDaily. Retrieved September 17, 2014 from www.sciencedaily.com/releases/2012/02/120212192552.htm
Whitehead Institute for Biomedical Research. "A mitosis mystery solved: How chromosomes align perfectly in a dividing cell." ScienceDaily. www.sciencedaily.com/releases/2012/02/120212192552.htm (accessed September 17, 2014).

Share This



More Plants & Animals News

Wednesday, September 17, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Some Tobacco Farmers Thrive Amid Challenges

Some Tobacco Farmers Thrive Amid Challenges

AP (Sep. 16, 2014) — The South's tobacco country is surviving, and even thriving in some cases, as demand overseas keeps growers in the fields of one of America's oldest cash crops. (Sept. 16) Video provided by AP
Powered by NewsLook.com
Scientists Given Rare Glimpse of 350-Kilo Colossal Squid

Scientists Given Rare Glimpse of 350-Kilo Colossal Squid

AFP (Sep. 16, 2014) — Scientists say a female colossal squid weighing an estimated 350 kilograms (770 lbs) and thought to be only the second intact specimen ever found was carrying eggs when discovered in the Antarctic. Duration: 00:47 Video provided by AFP
Powered by NewsLook.com
Raw: Scientists Examine Colossal Squid

Raw: Scientists Examine Colossal Squid

AP (Sep. 16, 2014) — Squid experts in New Zealand thawed and examined an unusual catch on Tuesday: a colossal squid. It was captured in Antarctica's remote Ross Sea in December last year and has been frozen for eight months. (Sept. 16) Video provided by AP
Powered by NewsLook.com
Ivorians Abandon Monkey Pets in Fear Over Ebola Virus

Ivorians Abandon Monkey Pets in Fear Over Ebola Virus

AFP (Sep. 16, 2014) — Since the arrival of Ebola in Ivory Coast, Ivorians have been abandoning their pets, particularly monkeys, in the fear that they may transmit the virus. Duration: 00:47 Video provided by AFP
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:
from the past week

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