Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

One for You, One for Me: Researchers Gain New Insight Into the Chromosome Separation Process

21.11.2011
Each time a cell divides—and it takes millions of cell divisions to create a fully grown human body from a single fertilized cell—its chromosomes have to be accurately divvied up between both daughter cells. Researchers at the Stowers Institute for Medical Research used, ironically enough, the single-celled organism Saccharomyces cerevisiae—commonly known as baker’s yeast—to gain new insight into the process by which chromosomes are physically segregated during cell division.

In a study published in the Nov. 17, 2011 issue of PLoS Genetics, they demonstrate that a protein known as Mps3 not only ensures that cells have two functional spindle pole bodies, which generate the mitotic spindle apparatus that helps pull the chromosomes apart, but also that both spindle pole bodies are properly anchored in the nuclear membrane.

“When you enter mitosis, you need to have two spindle pole bodies on which you can pull the chromosomes. If you don’t, the probability of errors in chromosome segregation increases exponentially,” explains Stowers assistant investigator Sue Jaspersen, Ph.D., adding that, “even small mistakes can lead to birth defects, genetic instability and cancer.”

Normally, cells have only a single spindle pole body, but in preparation for cell division, the spindle pole body has to duplicate itself – just as the genome does. “We know a whole lot about how DNA copies itself, but we don’t know much about how spindle pole bodies duplicate themselves,” says Jaspersen, who also holds an appointment as an assistant professor in the Department of Molecular and Integrative Physiology at the University of Kansas School of Medicine.

Unlike DNA molecules, which serve as templates for the production of identical copies, the spindle pole body is a large protein structure composed of soluble proteins and so-called integral membrane proteins, which are anchored in the nuclear envelope. The duplication process of the lone spindle pole body begins when soluble proteins coalesce on the nuclear envelope followed by their insertion into the lipid bi-layer located next to the original spindle pole body. Insertion probably requires the integral membrane proteins of the spindle pole body and results in a second functional spindle pole body.

While many genes are known to be required for spindle pole body duplication, the best studied are perhaps the conserved family of SUN-domain proteins. The SUN-protein homolog in yeast is Mps3, an integral membrane component of the spindle pole body required for early steps in the duplication process.

“Cells with little or no functional Mps3 do not divide, and have only one spindle pole body and one half of the mitotic spindle,” explains Jaspersen. “We were interested in how a spindle pole body gets inserted into the nuclear envelope, what modifications of this double lipid bi-layer membrane have to occur to facilitate insertion, and what is Mps3’s role in all of this?”

To better understand the function of Mps3 in spindle pole body duplication, Jaspersen’s team, led by co-first authors Jennifer Friederichs and Suman Ghosh, Ph.D., mutated specific regions of the Mps3 gene and then expressed the mutated genes in yeast. For most of the mutants, mitosis seemed normal. That wasn’t the case, however, with one particular novel mutant, MPS3-G186K, which has a small, “point” mutation in the so-called P-loop region.

The researchers next used high-resolution electron microscopy and various markers, including ones that can distinguish uninserted and inserted spindle pole bodies. What they saw was that, although their DNA had been duplicated, cells expressing this particular Mps3 mutant had multiple duplication defects, including blocking insertion of the spindle pole body into the nuclear envelope.

What was most striking, however, was that nearly every cell examined had nuclear membranes that were, essentially, overgrown—with two to eight layers of nuclear envelope, and multiple lobes and extensions—instead of a simple spherical structure. Importantly, the effect seemed specific in that the other membrane-based organelles appeared normal.

“We had never seen nuclei that looked like that,” recalls Jaspersen. “It suggested that Mps3 was regulating the lipid environment of the nuclear envelope, and that perhaps that was how it controlled spindle pole body insertion,” says Jaspersen.

To test their idea, the researchers expressed the MPS3-G186K mutant gene in a collection of yeast mutants, looking for ones that would fix the nuclear membrane defect. They found quite a few, and—as expected—two had mutations in genes that regulate cellular lipid content. When they treated cells with oleic acid (essentially lard), or by slightly increasing the growth temperature—presumably increasing membrane fluidity, they were able to suppress the defects.

“The nuclear envelope is not just a passive player but presumably is actively remodeled by Mps3 to accommodate the spindle pole body,” explains Jaspersen.

Besides their prominent role in mitosis, centrosomes, the higher eukaryotic equivalent of yeast spindle pole bodies, are required for making primary cilia—a hair-like appendage present in a single copy on every cell. At the base of primary cilia is a centrosome attached to the cell membrane that in cilia has a unique lipid composition. Jaspersen’s group is anxious to see what aspects of their Mps3 findings translate to primary cilia. If parallels exist, the rewards could be significant, since ciliary defects can lead to a number of human diseases—ranging from congenital heart failure to retinal degeneration.

Researchers who also contributed to the work include Christine Smoyer, Scott McCroskey, Brandon Miller, Kyle Weaver, Kym Delventhal, Jay Unruh and Brian Slaughter – all at the Stowers Institute for Medical Research in Kansas City Missouri. A collaboration with the Lipidomics Facility at Kansas State University was also integral to the project.

The work was funded in part by the Stowers Institute for Medical Research, the American Cancer Society, the M.R. & Evelyn Hudson Foundation, the National Science Foundation, the Kansas Technology Enterprise Corporation, K-IDeA Networks of Biomedical Research Excellence and the National Institutes of Health and Kansas State University.

About the Stowers Institute for Medical Research
The Stowers Institute for Medical Research is a non-profit, basic biomedical research organization dedicated to improving human health by studying the fundamental processes of life. Jim Stowers, founder of American Century Investments, and his wife Virginia opened the Institute in 2000. Since then, the Institute has spent over 800 million dollars in pursuit of its mission.

Currently the Institute is home to nearly 500 researchers and support personnel, over 20 independent research programs and more than a dozen technology development and core facilities. Learn more about the Institute at www.stowers.org (http://www.stowers.org).

Gina Kirchweger | Newswise Science News
Further information:
http://www.stowers.org

More articles from Life Sciences:

nachricht Ambush in a petri dish
24.11.2017 | Friedrich-Schiller-Universität Jena

nachricht Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: New proton record: Researchers measure magnetic moment with greatest possible precision

High-precision measurement of the g-factor eleven times more precise than before / Results indicate a strong similarity between protons and antiprotons

The magnetic moment of an individual proton is inconceivably small, but can still be quantified. The basis for undertaking this measurement was laid over ten...

Im Focus: Frictional Heat Powers Hydrothermal Activity on Enceladus

Computer simulation shows how the icy moon heats water in a porous rock core

Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

IceCube experiment finds Earth can block high-energy particles from nuclear reactions

24.11.2017 | Physics and Astronomy

A 'half-hearted' solution to one-sided heart failure

24.11.2017 | Health and Medicine

Heidelberg Researchers Study Unique Underwater Stalactites

24.11.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>