The intracellular protein Fyn-a suspect in the formation of neurofibrillary tangles because of its associations with tau protein-has now popped up in conjunction with prion diseases. Researchers in France report in tomorrow's Science that Fyn couples with the normal form of prion protein, an interaction that also involves the protein caveolin-1.

There is still no demonstrated function for the normal form of prion protein (as opposed to the abnormal form thought to cause transmissible spongiform encephalopathies such as mad cow disease and scrapie). The fact that it is localized in particularly high concentrations in the cell membranes of neurons has led to speculation that it is involved in signal transduction across the membrane. The current Science report adds fuel to that idea, finding that the normal prion protein is involved in an interactions with the intracellular tyrosine kinase Fyn. Because the two proteins are localized in different compartments, the researchers searched for an intermediate that might be able to link the two and found caveolin-1 involved in this cascade. (The protein clathrin, included as a control, also had some effect on the interaction, suggesting that it too may be involved.)

The researchers also noted that Fyn was not activated until the cultured cells had differentiated into neurons and that the signaling cascade seemed to only involve prion molecules located on neurites, and not on the cell body. Implicit in these results is the idea that an extracellular messenger must somehow be involved.-Hakon Heimer. (See William Klein's comment below on whether there might be some commonality in signal cascades in prion disease and in Alzheimer's.)

Reference:
Mouillet-Richard S, Ermonval M, Chebassier C, Laplanche JL, Lehmann S, Launay JM, Kellermann O. Signal transduction through prion protein. Science 2000 Sep 15;289(5486):1925-8. Abstract

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  1. Coupling of cellular prion proteins to Fyn is a real surprise, but
    maybe it shouldn't be. Fyn keeps popping up. Shirazi and Wood showed that tangle-bearing
    neurons in AD have a hefty overload of Fyn. Gloria Lee showed Fyn and tau co-localize.
    Gail Johnson's group showed that Fyn stimulates AD-like tau phosphorylation
    via GSK 3β. Kandel and Grant tied Fyn to LTP, and we found that Fyn knockout
    stops ADDL from killing neurons. That two neurodegenerative diseases both are
    linked in some way to Fyn reminds me of Wilson's concept of " consilience," coming
    to the same truth from very different pathways. I can imagine the gods of science
    saying, "Well, here's another clue for you… Now can you figure it out?"

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  1. . Signal transduction through prion protein. Science. 2000 Sep 15;289(5486):1925-8. PubMed.

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  1. . Signal transduction through prion protein. Science. 2000 Sep 15;289(5486):1925-8. PubMed.

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  1. . Signal transduction through prion protein. Science. 2000 Sep 15;289(5486):1925-8. PubMed.