Reporting in the November 23, 2011, issue of Cell the research team, led by Stowers investigator Rong Li, Ph.D., proposes that the limited mobility of clumps of damaged proteins and yeast cells’ geometry—the narrowness of the connection (bud neck) between the mother and the daughter before their separation, in particular—are sufficient to ensure that protein aggregates accumulated during the normal aging process are retained in the mother cell during cell division.
Cell (Nov. 23, 2011)
Image: Courtesy of Chuankai Zhou, Stowers Institute for Medical Research
The movements of protein aggregates found in old yeast cells follow a "random walk" pattern.
“Harmful protein aggregates had recently been thought to be sent back into the mother cell via a directed transport system,” says Li. “Our model suggests that no active shuttle mechanism may be necessary to help with the asymmetric segregation of protein aggregates during yeast cell divisions.”
In the budding yeast Saccharomyces cerevisae—an important model organisms used in aging research—lifespan can be defined by the number of daughter cells a mother has produced, as opposed to by calendar time, a process known as replicative aging. Daughter cells reset their clock and start counting the number of cell division they have undergone from scratch.
The transition from youth to old age is accompanied by metabolic changes and the accumulation of damage as a result of wear and tear. A central question in aging research is the nature of the damage that contributes to aging and how old mother cells avoid passing on these aging determinants to their daughters.
One factor that is known to correlate with replicative age is the buildup of aggregates formed by damaged proteins. “These proteins are preferentially retained by the mother during bud formation and cell division,” explains Li. “A better understanding of replicative aging of a cell population based on asymmetric cell divisions may provide insights into how higher organisms maintain a population of “youthful” stem cells with high proliferative potential during aging.“
To learn more about the movement and fate of damaged proteins in dividing yeast cells, graduate student and first author Chuankai Zhou with help from Amr Eldakak, Ph.D, a postdoctoral research associate in the Li laboratory, added a green fluorescent tag to Hsp104p, a protein known to modify and dissolve protein aggregates by unfolding and refolding proteins. Zhou then used live-cell imaging to record the movements of thousands of protein aggregates induced by heat in three dimensions.
“Most movements were confined within the bud or the mother but we did see a few movements from bud to mother and vice versa,” says Zhou. “Overall though, we couldn’t detect any directionality in the movements of the aggregates.” In order to rigorously characterize the movement of the protein aggregates, Zhou collaborated with Stowers Research advisors Brian Slaughter, Ph.D., and Jay Unruh, Ph.D., and used particle tracking and computational analysis to show that the aggregate movement is best described as ‘random walk’.
Time-lapse movies also revealed that, over time, heat shock-induced aggregates cleared from all buds and their numbers plummeted in mother cells. When Zhou introduced a mutation into Hsp104p that does not affect Hsp104p’s ability to bind to protein aggregates but disrupts its refolding activity, aggregates no longer cleared from neither mother nor daughter cell. “It told us that heat-induced aggregates dissolved with the help of Hsp104p,” explains Zhou.
Zhou then turned his attention to naturally occurring protein aggregates, which are the result of oxidative damage in cells of older replicative age. He found that these protein clumps followed the same random walk pattern but didn’t dissolve over time. However, these aggregates appeared to move within the confines of the mother without escaping into the bud.
With the help of Stowers research advisor Boris Rubinstein, the team used 3D numerical simulations as well as a 1D analytical model to show that the limited, random mobility of the aggregates was sufficient to explain their preferential retention in the mother, and that the narrow opening of the bud neck further helps trapping the aggregates within the mother prior to cell division.
The research was supported primarily by a grant from the National Institute of Health.
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 over 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.
Gina Kirchweger | Newswise Science News
A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
On the way to developing a new active ingredient against chronic infections
21.08.2017 | Deutsches Zentrum für Infektionsforschung
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,...
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...
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...
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...
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...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
21.08.2017 | Materials Sciences
21.08.2017 | Health and Medicine
21.08.2017 | Materials Sciences