Is prion a term used to describe the normal form of the protein as well as the disease causing form?

Question

I've been reading my textbook and it refers to prions as a normal protein with a helpful function but it can turn into a disease causing form. However, I look in my other textbook and it refers to the word prion as solely being a disease causing protein.

I'd like to know which is the correct definition. Ie. Would I be correct in saying "The prion protein is normally involved in synaptic transmission but can turn into a disease causing form"?

Thanks in advance!

Answer 1

The normal isoform of the protein is called PrP^C, which stands for cellular prion protein, while the infectious isoform is called PrP^SC, which stands for scrapie prion protein.

According to Riesner (2003):

The biochemical properties of the prion protein which is the major, if not only, component of the prion are outlined in detail. PrP is a host-encoded protein which exists as PrP^C (cellular) in the non-infected host, and as PrP^Sc (scrapie) as the major component of the scrapie infectious agent. (emphasis mine)

If you search for "cellular prion protein" you're gonna find several papers that use the name prion protein to the normal isoform. Some examples:

• Prado, M., Alves-Silva, J., Magalhães, A., Prado, V., Linden, R., Martins, V. and Brentani, R. (2004). PrPc on the road: trafficking of the cellular prion protein. Journal of Neurochemistry, 88(4), pp.769-781.
• Ramljak, S. (2008). Physiological function of the cellular prion protein (PrPc_1hnc). 1st ed. Berlin: Logos-Verl.
• Pantera, B., Bini, C., Cirri, P., Paoli, P., Camici, G., Manao, G. and Caselli, A. (2009). PrP^c activation induces neurite outgrowth and differentiation in PC12 cells: role for caveolin-1 in the signal transduction pathway. Journal of Neurochemistry, 110(1), pp.194-207.
• Martins, V., Mercadante, A., Cabral, A., Freitas, A. and Castro, R. (2017). Insights into the physiological function of cellular prion protein.

And many others.

Therefore, following this nomenclature, the answer to your question ("Would I be correct in saying 'The prion protein is normally involved in synaptic transmission but can turn into a disease causing form'?") is yes. The difference is the adjective: cellular or scrapie.

Finally, pay attention to this: you have two different questions here. In the title you say "Is prion a term used...", but in the last paragraph you say ""Is the prion protein normally involved in...". As extensively discussed in the other answer, the term prion alone (instead of prion protein) is normally used only when referring to the abnormal isoform. More on that here: https://www.cdc.gov/prions/pdfs/public-health-impact.pdf

Source: Detlev Riesner; Biochemistry and structure of PrPC and PrPSc. Br Med Bull 2003; 66 (1): 21-33.

Answer 2

If we are considering prions in general, I disagree with the answer supplied by Gerardo Furtado.

Here is a definition taken from an article by Susan Lindquist:

[Prions are]...self-perpetuating and heritable protein conformations that cause multiple phenotypes, represent an unusual mechanism of information transfer that occurs via protein instead of nucleic acid.

Compare Wikipedia:

Prions are infectious agents...

If a prion is self-perpetuating or infectious then the normal form of such a protein is not a prion. In yeast the term prion is used to refer to the infectious form of a protein in a formal genetic sense. For example the [PSI⁺] prion was discovered as a genetic element and then subsequently found to be associated with the translation termination factor Sup35, a protein with a known cellular role. All yeast strains have Sup35 protein but only certain strains contain and transmit the prion form of this protein. So [PSI⁺] is referred to as the prion form of the protein.

The problem with interpreting the language used to describe the TSE prions is that they were discovered because of their prion activity so the normal form is referred to as prion protein (as far as I am aware the function of the normal form isn't known). This doesn't mean that this form of the protein IS a prion, merely that this protein is associated with the original prion phenomenon so is called 'prion protein'.

Answer 3

The Wikipedia definition of prions is quite clear I think:

Prions are infectious agents composed entirely of a protein material that can fold in multiple, structurally abstract ways, at least one of which is transmissible to other prion proteins, leading to disease in a manner that is epidemiologically comparable to the spread of viral infection.

Your definition: "The prion protein is normally involved in synaptic transmission but can turn into a disease causing form" it is misleading. First, it sounds like there is a protein called prion that is involved in synaptic transmission, which is not true. Prions are a subset of the group proteins. Moreover, not all the prions are derived from proteins involved in the synaptic transmission. Prions have been found in other organisms like bacteria and fungi, so there is little to do with synaptic transmission there. The wiki page I have linked is full of links to the related literature, start there your journey!