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How To Remember Without a Brain

October 2, 2012

Single celled beasts like the yeast S. cerevisiae can “remember” previous insults and so respond better to environmental changes in the future. For example, a yeast cell treated with 0.7M NaCl will respond better in the future to hydrogen peroxide. Not only that but so will its daughters, granddaughters and even its great, great granddaughters.

Who needs a brain to remember things?

In a new study out in GENETICS, Guan and coworkers show at least a couple of ways that this can happen. One is what anyone in biology might expect these days (although with an interesting twist). The NaCl treatment causes a rewiring of the regulatory network at an epigenetic level and this affects future responses to environmental insults.

But fancy epigenetic changes aren’t the only way that yeast remembers things.  No, it also uses a simple, elegant solution—protein stability.
 
Long Live The Protein!
 

The researchers did a set of experiments that showed that a yeast’s memory of a salt treatment did not rely on new protein synthesis and that it slowly faded with each generation.  One possible explanation was that the salt induced a stable factor that was divvied up and diluted with each passing generation. Guan and coworkers found that this was the case and that at least one of these factors was the cytosolic catalase 1 protein, Ctt1p.

The cytosolic catalase 1 or CTT1 gene is induced by salt but quickly returns to normal levels when the salt is removed.  However, Ctt1p is so long lived that it hangs around for at least six hours.  In that time the yeast has budded off multiple daughters, all of which are still better at dealing with hydrogen peroxide than their untreated sisters.

What a marvelously simple way to adapt!  Just make something that hangs around a long time and you and your kids will do better when the next insult comes.  The elegance of evolution.

This explains in part how yeast cells can remember the salt treatment of their ancestors, but a single long-lived protein isn’t the whole story.  No, there is something a bit more complicated going on at the nuclear pore too.

 
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Guan and coworkers looked at the gene expression pattern of salt stressed and naïve yeast when exposed to hydrogen peroxide.  They found that 449 genes responded more quickly to hydrogen peroxide treatment if the cell had been pretreated with salt.  Importantly, 51 of these hadn’t reacted previously to the salt treatment, meaning that previous activation wasn’t required.

One idea is that these genes are more accessible to transcription because they are associated with the nuclear pore.  The idea is that faster response happens because the gene is closer to the nuclear envelope and/or because it has been looped near some sort of activator.

This is what has been proposed with inositol starvation and it looks like it may be true here too.  In both cases, eliminating Nup42p, a nuclear pore protein, eliminates the more rapid response to hydrogen peroxide.

So in this case it looks like cells can remember a previous insult with just a long-lived protein and a bit of genetic rewiring.  It will be interesting to see how universal these sorts of mechanisms are for cell memory.

by D. Barry Starr, Ph.D., Director of Outreach Activities, Stanford Genetics