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.)
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