Featured Research

from universities, journals, and other organizations

Protective prion keeps yeast cells from going it alone

Date:
March 28, 2013
Source:
Whitehead Institute for Biomedical Research
Summary:
A team of scientists has added markedly to the job description of prions as agents of change, identifying a prion capable of triggering a transition in yeast from its conventional single-celled form to a cooperative, multicellular structure. This change, which appears to improve yeast's chances for survival in the face of hostile environmental conditions, is an epigenetic phenomenon -- a heritable alteration brought about without any change to the organism’s underlying genome.

Most commonly associated with such maladies as "mad cow disease" and Creutzfeldt-Jakob disease, prions are increasingly recognized for their ability to induce potentially beneficial traits in a variety of organisms, yeast chief among them.

Now a team of scientists has added markedly to the job description of prions as agents of change, identifying a prion capable of triggering a transition in yeast from its conventional single-celled form to a cooperative, multicellular structure. This change, which appears to improve yeast's chances for survival in the face of hostile environmental conditions, is an epigenetic phenomenon -- a heritable alteration brought about without any change to the organism's underlying genome.

This latest finding, reported in the March 28 issue of the journal Cell, has its origins in work begun several years ago in the lab of Whitehead Institute Member Susan Lindquist. In 2009, Randal Halfmann, then a graduate student in Lindquist's lab, identified dozens of proteins in yeast that have the ability to form prions. That research greatly expanded the known universe of prion elements in yeast, but it failed to answer a key question: What function, if any, do these prions actually have?

In search of an answer, Halfmann, now a fellow the University of Texas Southwestern Medical Center, and colleagues in the Lindquist lab attempted to exploit the fact that several of the prion-forming proteins they had identified acted to modify transcription of yeast genes. It stood to reason that if they could identify which genes were being regulated, they might be able to determine the prions' function.

"We looked at the five transcriptional regulators that are known to be prions in yeast, and we found that in fact, only one gene in the entire yeast genome was regulated by all five transcription factors," says Halfmann.

That gene, as it turns out, was FLO11, a key player in multicellularity in yeast. Indeed changes in FLO11 expression have been shown to act as a toggle, switching yeast from spherical to filamentous form. Halfmann notes that FLO11, which has been shown to be regulated by epigenetic elements, is also highly responsive to environmental stress. Knowing that the prion form of a protein is essentially a misfolded form of that protein, and that stressful conditions increase the frequency of protein misfolding and prion formation, the scientists began to consider the possibility that the prions themselves might be among the epigenetic switches influencing the activity of FLO11.

The group focused on one transcription factor known as mot3, finding that yeast cells containing the prion form of this factor, [MOT3+], acquired a variety of multicellular growth forms known to require FLO11 expression. This was a clear indication that prion formation was causing the differentiation of the cells and their subsequent cooperation. But what about the stress aspect of the hypothesis?

By testing yeast cells against a variety of stressors, the scientists discovered that exposure to a concentration of ethanol akin to that occurring naturally during fermentation increased [MOT3+] formation by a factor of 10.They also found that as the cells exposed to ethanol shifted their metabolism to burn surrounding oxygen through respiration, the prions reverted to their non-prion conformation, [mot3-], and the yeast returned to the unicellular state. In essence, prion formation drove a shift to multicellularity, helping the yeast to ride out the ethanol storm.

"What we have in the end is two sequential environmental changes that are turning on a heritable epigenetic element and then turning it off," says Halfmann. "And between those two changes, the prion is causing the cells to acquire a multicellular growth form that we think is actually important for their survival."

Lindquist, who is also a Howard Hughes Medical Institute investigator, has long argued that prions have played a vital role in yeast evolution and has amassed a body of strong supporting evidence.

"We see them as part of a bet-hedging strategy that allows the yeast to alter their biological properties quickly when their environments turn unfavorable," Lindquist says. She also theorizes that prions may play such roles beyond yeast, and her lab intends to take similar approaches in the hunt for prions and prion-like mechanisms that are potentially beneficial in other organisms.

For Lindquist lab postdoctoral scientist Alex Lancaster, who is also an author of the new Cell paper, these latest findings hint at a potentially novel approach to understanding basic mechanisms underlying the complexities of human diseases, including cancer, whose hallmarks include protein misfolding, epigenetic alterations, metabolic aberrations, and myriad changes in cell state, type, and function. Lancaster likens the opportunity to that of opening a black box.

"It's exciting to think that this could become another tool in the toolbox in the study of multicellularity," Lancaster says. "We know that some tumors are a heterogeneous population of cells and we know that tumor cells can evolve within in their environments to help ensure their own survival. This system could help us further understand the role of epigenetic inheritance within tumors and how it might be influencing cell-cell interactions and even affecting the effectiveness of drug therapies."

This work was supported by grants from the National Institutes of Health, the G. Harold and Leila Y. Mathers Foundation and Howard Hughes Medical Institute.


Story Source:

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


Journal Reference:

  1. DanielL. Holmes, AlexK. Lancaster, Susan Lindquist, Randal Halfmann. Heritable Remodeling of Yeast Multicellularity by an Environmentally Responsive Prion. Cell, 2013; 153 (1): 153 DOI: 10.1016/j.cell.2013.02.026

Cite This Page:

Whitehead Institute for Biomedical Research. "Protective prion keeps yeast cells from going it alone." ScienceDaily. ScienceDaily, 28 March 2013. <www.sciencedaily.com/releases/2013/03/130328142139.htm>.
Whitehead Institute for Biomedical Research. (2013, March 28). Protective prion keeps yeast cells from going it alone. ScienceDaily. Retrieved September 18, 2014 from www.sciencedaily.com/releases/2013/03/130328142139.htm
Whitehead Institute for Biomedical Research. "Protective prion keeps yeast cells from going it alone." ScienceDaily. www.sciencedaily.com/releases/2013/03/130328142139.htm (accessed September 18, 2014).

Share This



More Plants & Animals News

Thursday, September 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Chimp Violence Study Renews Debate On Why They Kill

Chimp Violence Study Renews Debate On Why They Kill

Newsy (Sep. 17, 2014) The study weighs in on a debate over whether chimps are naturally violent or become that way due to human interference in the environment. Video provided by Newsy
Powered by NewsLook.com
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

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