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In Flies, a Prion-Like Protein Helps Maintain Long-Term Memories

By Sarah Zhang
Feb 8, 2012 7:08 PMNov 20, 2019 2:31 AM


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What's the News: When prions or amyloids make the news, it's usually because they cause mad cow disease

 or Alzheimer's


, after all, cause any proteins they touch to become as misfolded as they are, and amyloids

, which are large clumps of wadded-together proteins, can jam the workings of cells. But a new study in Cell suggests that a prion-like protein that forms amyloids has a normal, vital function in the brain

. Far from being a memory destroyer, this protein, called CPEB, is necessary for long-term memory in fruit flies.How the Heck:

  • To see where the protein resides in the brain, the researchers added a fluorescent tag to the fruit fly version of CPEB, which is called Orb2A. They observed that Orb2A formed amyloids at synapses, the junctions between neurons---a promising sign that it could be involved in memory.

  • To see whether Orb2A was actually necessary for memory, the researchers created fly mutants with a defective version of Orb2A. A single amino acid was changed, but that was enough to prevent the formation of amyloids.

  • It was also enough to disrupt the flies' long-term memory, the team found. As a test of memory, flies had been taught to associate a particular smell with a squirt of sugar water, and at first, the mutant flies chose the reward-associated smell as just often as normal flies. 48 hours later, though, the mutants suddenly got much worse at the task.

  • Orb2A, thus, seems to be involved in maintaining memories over time.

What's the Context:

  • The researchers already suspected that CPEB had a role in long-term memory, after a previous study in sea slugs suggested the two were linked: disrupting CPEB's amyloids kept sea slugs' neurons from undergoing long-term potentiation, which is similar to long-term memory. But it's interesting to see that CPEB is also at work in the much more complex brains of fruit flies.

  • Over at The Frontal Cortex, Jonah Lehrer writes about a potential mechanism for CPEB in long-term memory. The prion-like protein marks any synapse involved in long-term memory, acting perhaps as a stop sign that prevents the connection from changing and the memory eroding.

The Future Holds:

  • How prions behave in various tissues and situations is a topic of active research---they were discovered only 20 years ago, and there's a lot about them we don't know. As this study suggests, it's possible that certain prions have a perfectly normal function in the brain. Future studies will need to pin down the mechanism of how CPEB actually works at a synapse to preserve long-term memory.

Reference: Majumdar, et al. Critical Role of Amyloid-like Oligomers of Drosophila Orb2 in the Persistence of Memory. Cell 148, 515-529 (3 February 2012) DOI 10.1016/j.cell.2012.01.004

[via The Frontal Cortex


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