Featured Research

from universities, journals, and other organizations

What makes memories last? Prion-like proteins help create long-term memories

Date:
February 11, 2014
Source:
Stowers Institute for Medical Research
Summary:
Prions can be notoriously destructive, spurring proteins to misfold and interfere with cellular function as they spread without control. New research reveals that certain prion-like proteins, however, can be precisely controlled so that they are generated only in a specific time and place. These prion-like proteins are not involved in disease processes; rather, they are essential for creating and maintaining long-term memories.

Fruit flies have co-opted a self-sustaining prion switch as a key mechanism for the persistence of memories. When TOB (shown in green) binds to Orb2A (shown in red), it triggers Orb2A conversion to a stable prion state (shown in yellow). Orb2A's activity is tightly controlled through its interaction with TOB, which is triggered by incoming nerve signals.
Credit: Nicolle Rager Fuller, Sayo-Art

Prions can be notoriously destructive, spurring proteins to misfold and interfere with cellular function as they spread without control. New research, published in the open access journal PLOS Biology on February 11, 2014, from scientists at the Stowers Institute for Medical Research reveals that certain prion-like proteins, however, can be precisely controlled so that they are generated only in a specific time and place. These prion-like proteins are not involved in disease processes; rather, they are essential for creating and maintaining long-term memories.

Related Articles


"This protein is not toxic; it's important for memory to persist," says Stowers researcher Kausik Si, Ph.D., who led the study. To ensure that long-lasting memories are created only in the appropriate neural circuits, Si explains, the protein must be tightly regulated so that it adopts its prion-like form only in response to specific stimuli. He and his colleagues report on the biochemical changes that make that precision possible.

Si's lab is focused on finding the molecular alterations that encode a memory in specific neurons as it endures for the days, months, or years -- even as the cells' proteins are degraded and renewed. Increasingly, their research is pointing toward prion-like proteins as critical regulators of long-term memory.

In 2012, Si's group demonstrated that prion formation in nerve cells is essential for the persistence of long-term memory in fruit flies. Prions are a fitting candidate for this job because their conversion is self-sustaining: once a prion-forming protein has shifted into its prion shape, additional proteins continue to convert without any additional stimulus.

Si's team found that in fruit flies, the prion-forming protein Orb2 is necessary for memories to persist. Flies that produce a mutated version of Orb2 that is unable to form prions learn new behaviors, but their memories are short-lived. "Beyond a day, the memories become unstable. By three days, the memory has completely disappeared," Si explains.

In the new study, Si wanted to find out how this process could be controlled so that memories form at the right time. "We know that all experiences do not form long-term memory -- somehow the nervous system has a way to discriminate. So if prion-formation is the biochemical basis of memory, it must be regulated." Si says. "But prion formation appears to be random for all the cases we know of so far."

Si and his colleagues knew that Orb2 existed in two forms -- Orb2A and Orb2B. Orb2B is widespread throughout the fruit fly's nervous system, but Orb2A appears only in a few neurons, at extremely low concentrations. What's more, once it is produced, Orb2A quickly falls apart; the protein has a half-life of only about an hour.

"When Orb2A binds to the more abundant form, it triggers conversion to the prion state, acting as a seed for the conversion. Once conversion begins, it is a self-sustaining process; additional Orb2 continues to convert to the prion state, with or without Orb2A. By altering the abundance of the Orb2A seed," Si says, "cells might regulate where, when, and how the conversion process is engaged." But how do nerve cells control the abundance of the Orb2A seed?

Their experiments revealed that when a protein called TOB associates with Orb2A , it becomes much more stable, with a new half-life of 24 hours. This step increases the prevalence of the prion-like state and explains how Orb2's conversion to the prion state can be confined in both time and space.

The findings raise a host of new questions for Si, who now wants to understand what happens when Orb2 enters its prion-like state, as well as where in the brain the process occurs. While unraveling these mechanisms will likely be more accessible in the fruit fly than in more complex organisms, Si points out that proteins related to Orb2 and TOB have also been found in the brains of mice and humans. He has already shown that in the sea snail Aplysia, conversion to a prion-like state facilitates long-term change in synaptic strength. "This basic mechanism appears to be conserved across species," he notes.

Researchers who also contributed to the work include Liying Li and Repon Mahammad Khan in the Department of Molecular and Integrative Physiology at the University of Kansas Medical Center, and Erica White- Grindley, Fengzhen Ren, Anita Saraf and Laurence Florens at the Stowers Institute for Medical Research.

The research was funded by the Stowers Institute for Medical Research.


Story Source:

The above story is based on materials provided by Stowers Institute for Medical Research. Note: Materials may be edited for content and length.


Journal Reference:

  1. Erica White-Grindley, Liying Li, Repon Mohammad Khan, Fengzhen Ren, Anita Saraf, Laurence Florens, Kausik Si. Contribution of Orb2A Stability in Regulated Amyloid-Like Oligomerization of Drosophila Orb2. PLoS Biology, 2014; 12 (2): e1001786 DOI: 10.1371/journal.pbio.1001786

Cite This Page:

Stowers Institute for Medical Research. "What makes memories last? Prion-like proteins help create long-term memories." ScienceDaily. ScienceDaily, 11 February 2014. <www.sciencedaily.com/releases/2014/02/140211174613.htm>.
Stowers Institute for Medical Research. (2014, February 11). What makes memories last? Prion-like proteins help create long-term memories. ScienceDaily. Retrieved December 21, 2014 from www.sciencedaily.com/releases/2014/02/140211174613.htm
Stowers Institute for Medical Research. "What makes memories last? Prion-like proteins help create long-term memories." ScienceDaily. www.sciencedaily.com/releases/2014/02/140211174613.htm (accessed December 21, 2014).

Share This


More From ScienceDaily



More Mind & Brain News

Sunday, December 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Buzz60 (Dec. 19, 2014) A double-amputee makes history by becoming the first person to wear and operate two prosthetic arms using only his mind. Jen Markham has the story. Video provided by Buzz60
Powered by NewsLook.com
Prenatal Exposure To Pollution Might Increase Autism Risk

Prenatal Exposure To Pollution Might Increase Autism Risk

Newsy (Dec. 18, 2014) Harvard researchers found children whose mothers were exposed to high pollution levels in the third trimester were twice as likely to develop autism. Video provided by Newsy
Powered by NewsLook.com
Yoga Could Be As Beneficial For The Heart As Walking, Biking

Yoga Could Be As Beneficial For The Heart As Walking, Biking

Newsy (Dec. 17, 2014) Yoga can help your weight, blood pressure, cholesterol and heart just as much as biking and walking does, a new study suggests. Video provided by Newsy
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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