Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Molecular forces are key to proper cell division

22.01.2013
Studies led by cell biologist Thomas Maresca at the University of Massachusetts Amherst are revealing new details about a molecular surveillance system that helps detect and correct errors in cell division that can lead to cell death or human diseases

Studies led by cell biologist Thomas Maresca at the University of Massachusetts Amherst are revealing new details about a molecular surveillance system that helps detect and correct errors in cell division that can lead to cell death or human diseases. Findings are reported in the current issue of the Journal of Cell Biology.


This shows the expression of the chromokinesin NOD (red) stabilizes aberrant interactions between kinetochores and spindle microtubules (green). Tension stabilizes bioriented attachments where each sister chromatid is attached to microtubules from opposite spindle poles while tensionless attachments are typically unstable and corrected. Elevating the polar ejection force that pushes chromosome arms away from spindle poles overwhelms error correction, resulting in a dose-dependent stabilization of syntelic attachments where sister chromatids are attached to the same spindle pole.

Credit: Thomas Maresca, UMass AMherst

The purpose of cell division is to evenly distribute the genome between two daughter cells. To achieve this, every chromosome must properly interact with a football-shaped structure called the spindle. However, interaction errors between the chromosomes and spindle during division are amazingly common, occurring in 86 to 90 percent of chromosomes, says Maresca, an expert in mitosis.

"This is not quite so surprising when you realize that every single one of the 46 chromosomes has to get into perfect position every time a cell divides," he notes. The key to flawless cell division is to correct dangerous interactions before the cell splits in two.

Working with fruit fly tissue culture cells, Maresca and graduate students Stuart Cane and Anna Ye have developed a way to watch and record images of the key players in cell division including microtubule filaments that form the mitotic spindle and sites called kinetochores that mediate chromosome-microtubule interactions. They also examined the contribution of a force generated by molecular engines called the polar ejection force (PEF), which is thought to help line up the chromosomes in the middle of the spindle for division. For the first time, they directly tested and quantified how PEF, in particular, influences tension at kinetochores and affects error correction in mitosis.

"We also now have a powerful new assay to get at how this tension regulates kinetochore-microtubule interactions," Maresca adds. "We knew forces and tension regulated this process, but we didn't understand exactly how. With the new technique, we can start to dissect out how tension modulates error correction to repair the many erroneous attachment intermediates that form during division."

The cell biologists conduct their experiments inside living cells. In normal cell division, chromosomes line up in the center, where two copies of each chromosome are held together with "molecular glue" until signaled to dissolve the glue and divide. To oversimplify, each chromosome copy is then pulled to opposite poles of the cell, escorted in what looks like a taffy pull away from the center as two new daughter cells are formed.

During the split, molecular engines pull the copies apart along microtubule tracks that take an active role in the process that includes shortening microtubules by large, flexible scaffold-like protein structures called kinetochores that assemble on every chromosome during division. Maresca and colleagues say until this study revealed details, PEF's function as a kinetochore regulator has been underappreciated.

Overall, this well orchestrated process prevents serious problems such as aneuploidy, that is, too many chromosomes in daughter cells. Aneuploidy in somatic or body cells leads to cell death and is a hallmark of most cancer cells. But in eggs or sperm, it leads to serious birth defects and miscarriages.

In properly aligned division, microtubules from opposite spindle poles tug chromosome copies toward opposite poles, but they stick together with molecular glue until the proper moment. This creates tension at the kinetochores and stabilizes their interactions with microtubules. However, if attachments are bad, or syntelic, both copies attach to the same pole, leading to chromosome mis-segregation and aneuploidy if uncorrected. "Cells have a surveillance mechanism that allows them to wait for each for every chromosome to properly align before divvying up the chromosomes," Maresca says. "It's clear in our movies that the cell waits for the last kinetochores to correctly orient before moving forward."

To study this at the molecular level, Maresca and colleagues designed experiments to trick the cellular machinery into overexpressing the molecular engine that produces PEF. Surprisingly, this caused a dramatic increase in a type of bad kinetochore-microtubule interaction called syntelic attachments. They also fluorescently tag chromosomes, microtubules, kinetochores and the molecular engine kinesin with different colors to visualize interactions in real time using a special microscope at UMass Amherst able to image single molecules. Quantifying the amount of fluorescence of the force-producing molecular engine, they were able to assess the relative strength of the PEF in cells.

Maresca says, "We see the detection pathway preventing the molecular glue from dissolving until every chromosome is correctly aligned. The delay gives the cell time to correct errors. We propose that these bad syntelic attachments are normally very short-lived because they are not under proper tension. However, when we experimentally elevate PEF, tension is introduced at attachments that do not typically come under tension, essentially tricking the cell into thinking these chromosomes are properly aligned."

Plotting the percent of syntelic attachments versus the amount of PEF, Maresca and colleagues observed an error rate that plateaus at 80 to 90 percent, mirroring and supporting earlier work by others in different cell types. "In cells with elevated PEFs, the correction pathway is overridden, the detection mechanism is silenced and the result is disastrous because it leads to severe aneuploidy. This research has taught us about how an important molecular engine generates the PEF and how this force affects the accuracy of cell division."

Janet Lathrop | EurekAlert!
Further information:
http://www.umass.edu

More articles from Life Sciences:

nachricht A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>