A prion consists of a single infective protein. Unlike other pathogens, nucleic acid isn't necessary to make future generations. Instead, a prion is capable of making more of itself by converting a particular host protein (called prion protein- PrP) into a prion. In essence, the prion protein functions to change the conformation of PrP such that it now takes on the function of a prion; these converted prions in turn recruit others. Most of the pathogenicity occurs because these prions also form aggregates in cells of the brain, ultimately resulting in death.
Prions, as we know them, are dangerous, but because PrP can be so easily converted into a prion, many groups have begun asking, "What function does normal PrP have inside a cell?” Or more generally, what are these potential prions doing there?
Eleven prions have been identified in yeast so far and are a good place to start for finding out what these things do. Interestingly, a new paper published in Nature Cell Biology (http://www.nature.com/ncb/) by Dr. Susan W. Liebman's group at the University of Illinois Chicago has discovered another method of non-Mendelian inheritance via prion function (note: this is my take, the paper is more scientifically conservative and accurate in that its title is The yeast global transcriptional co-repressor protein Cyc8 can propagate as a prion).
It's a good paper and there's a insightful comment on it in the issue, so I won't go into much detail here, but I did want to list a few key points.
Cyc8 (called OCT in its prion form) is a global transcriptional co-repressor protein that, among other things, regulates yeast growth on lactate. This protein suppresses other proteins important for growth on lactate plates. However, by transiently overexpressing the putative prion domain of Cyc8 (and thus increasing the chance of misfolding for the naturally occurring Cyc8) , the authors were able to show increased colonies growing on lactate plates versus controls. The authors were then able to do further experiments using this Lac+ phenotype
One of the most important things they did was an experiment to show that these Lac+ colonies were not spontaneous mutations resulting in revertants. (i.e. mutated nonfunctional Cyc8). Overexpression of functional Cyc8 did not restore the Lac+ phenotype.
However, as an aside, there was always the possibility of a gain-of-function mutation. Perhaps the gene required for lactate growth lost its ability to be repressed by Cyc8. I feel that simple sequencing of the most important genes involved in the Lac+ pathway could have been useful, but the authors’ main concern was elsewhere and they focused their remaining experiments in proving that OCT has all the characteristics of a prion.
This was the most fundamental, and convincing, aspect of the paper. The OCT+ mutation was dominant in an OCT- cross (not characteristic of Cyc8 loss mutations), cytoplasm of OCT+ cells could transfer the Lac+ growth phenotype, and fluorescence of OCT fused to YFP showed aggregates within the cells.
This paper continues to extend the knowledge of prion function. They ain't just fer disease anymore! Instead, proteins with prion-like characteristics might serve to regulate cell function in a rapid and inherited manner, without the need to continuously monitor transcriptional and translational levels of mRNA. (In fact, this paper cites other work with the prion Swi, a protein involved in chromatin remodeling.)
While this paper involves propagation of OCT and didn't look at any possible regulation of Cyc8 to OCT conversion, the fact that there are 11 putative prions in yeast is suggestive. Instead of relying on mutation and unchangeable consequences, perhaps some prion-like proteins can be converted between the two states. (The paper might have a citation on this; I'll need to check it out further)
Again, if you're really interested, check out the paper:
Patel B.K., Gavin-Smyth J., and S.W. Liebman. The yeast global transcriptional co-repressor protein Cyc8 can propagate as a prion. Nature Cell Biology. March 11, 2009. DOI: 10.1038/ncb1843
http://www.ncbi.nlm.nih.gov/pubmed/19219034
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