Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers track protein 'hitchhiker' in fluorescent worms

07.04.2015

Understanding healthy cell division could have implications for cancer patients, embryos

Dividing cells--whether they're in an embryo or an adult--rely on the right processes happening at the right time to turn out healthy.


Lab photographs of the dividing cells are shown. The round, sun-like structures in each cell are the centrosomes. The fluorescent-tagged beta-catenin is the singular, oblong structure of contrasting color.

Photo courtesy of Bryan Phillips.

Now, researchers at the University of Iowa have identified a mechanism that dividing cells in worms use to ensure their proper development, and they believe the same process could be going on in humans. The mechanism, unknown until now, describes one part of the cell, called the centrosome, as an "internal timekeeper"--like a train conductor. A crucial protein in charge of gene expression, beta-catenin, is described as a "hitchhiker"--it jumps onboard the cellular train and helps cells grow the way they should.

The researchers believe that the hitchhiker protein attaches to the timekeeping centrosome, only so that it can be properly regulated and divided out in the correct amounts to the newly forming cells.

"The majority of tumors have severe centrosome abnormalities," says UI integrated biology doctoral candidate and first author Setu Vora. "So it's entirely possible that this kind of mechanism at the centrosome may be relevant in human diseases, such as cancer."

The researchers believe their discovery could have implications for cancer research, and lend greater understanding to how we develop.

"We think it's crucial to understand how these basic mechanisms work in order to better understand human development and disease," says Bryan Phillips, UI assistant professor of biology and corresponding author.

The Timekeeper's Mechanism

A key part of all animal cells, the centrosome, acts as the cell division captain--it is responsible for making sure new cells get equal portions of DNA when they are created. Now, the UI researchers say, the centrosome also acts as the timekeeper during cell division, specifically for another crucial member in the process, beta-catenin.

Beta-catenin is a protein that controls gene expression. Basically, it is present during cell division but starts to degrade, limiting how much of itself is given to the daughter cells. How much beta-catenin each cell gets during division helps to determine what kind of cell it is: arm, leg, liver, or otherwise. The researchers found that beta-catenin only knows how much of itself to give out to newly forming cells because it attaches to the centrosome--this is where the centrosome's timekeeper responsibilities come in.

Centrosomes mature and grow inside of cells just as the cells start to divide. It might seem counterintuitive to have a crucial part of a cell become active just before the cell is splitting apart, but it means that a mature centrosome could serve as an internal indicator that the cell is about to divide. At that same moment, beta-catenin attaches itself to the centrosome, like a hitchhiker, Phillips says. Attached, the Timekeeper and the Hitchhiker start to work together.

Lab photographs of dividing cells

Lab photographs of the dividing cells. The round, sun-like structures in each cell are the centrosomes. The fluorescent-tagged beta-catenin is the singular, oblong structure of contrasting color. Photo courtesy of Bryan Phillips.

Because of its hitchhiking ability, the two newly forming daughter cells inherit little beta-catenin. This allows for tight control of the levels of newly formed beta-catenin; one cell can then accumulate low beta-catenin levels, and one high levels. The difference in beta-catenin will dictate what kind of tissue the cells will become. The centrosome, with its eye on the clock, lets this process go on just long enough for the new cells to get as much beta-catenin as each one needs to become the properly functioning tissue it is supposed to be, before the centrosome and beta-catenin detach, and the process ends.

The Method, and Beyond

The researchers were able to track the entire mechanism in their model system, a transparent roundworm called C. elegans. They used a well-known technique to put a fluorescent tag on the beta-catenin proteins into the worm, and they could monitor the process under a fluorescent microscope. The researchers inserted a manipulated piece of DNA into the genome of the worm, consisting of the information that encodes the protein, and also the information that encodes the fluorescent tag. That way, every time the worm produced more of the protein, it showed up as a fluorescent green dot.

Those collections of dots got brighter the more beta-catenin was in one area, and the researchers could measure the intensity of that fluorescent light in each cell with a charge-coupled device (CCD) camera attached to their microscope. That allowed them to not only see that the beta-catenin was attached to the centrosome, but also, how much of it was being produced.

As it turns out, the only reason beta-catenin attaches to the centrosome at all is to be regulated, the researchers say. When they blocked beta-catenin's ability to hitchhike on the centrosome, the daughter cells that were supposed to receive low levels of beta-catenin ended up with too much. Some of those cells end up converting to completely different tissue types.

The study, "Centrosome-Associated Degradation Limits beta-catenin Inheritance by Daughter Cells after Asymmetric Division," presented in April in the journal Current Biology, has implications for the growth of cancer cells, Phillips says.

"In adults, this might be important because we need to keep beta-catenin levels regulated in stem cells. If there is too much beta-catenin in our stem cells, the cells can divide too quickly and may become cancerous," Phillips says.

Beta-catenin regulation is clinically important. Nearly all intestinal tumors involve some measure of beta-catenin regulation defect, and early birth defects involving beta-catenin result in miscarriage. Additionally, beta-catenin helps early embryonic patterning decisions in mammals, including core pathways involved in development of limbs, Phillips says.

Continuing to study the centrosome with the understanding of this mechanism, and how proteins are distributed to new cells, could lead to crucial new medical information. It is a couple steps out from this initial discovery, but the mechanism opens the door to a world of understanding about our cells, Phillips says.

###

The study was funded through a grant from the American Cancer Society and the Holden Comprehensive Cancer Center, a grant from the Roy J. Carver Charitable Trust, and an Evelyn Hart Watson fellowship.

Media Contact

Brittany Borghi
brittany-borghi@uiowa.edu
319-384-0048

 @UIowaResearch

http://www.uiowa.edu 

Brittany Borghi | EurekAlert!

More articles from Life Sciences:

nachricht Biofuel produced by microalgae
28.02.2017 | Tokyo Institute of Technology

nachricht Decoding the genome's cryptic language
27.02.2017 | University of California - San Diego

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Safe glide at total engine failure with ELA-inside

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded after a glide flight with an Airbus A320 in ditching on the Hudson River. All 155 people on board were saved.

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded...

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Scientists reach back in time to discover some of the most power-packed galaxies

28.02.2017 | Physics and Astronomy

Nano 'sandwich' offers unique properties

28.02.2017 | Materials Sciences

Light beam replaces blood test during heart surgery

28.02.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>