Altered membrane distribution and increased Fyn activity in scrapie-infected neuronal cells
(English)Manuscript (preprint) (Other academic)
The suggested cause of Prion diseases is conversion of the cellular prion protein (PrPC) into aberrant scrapie prion protein (PrPSc) isoform triggered by the latter. PrPC is localized to membrane rafts, subdomains which are implicated in conversion. In this report we have analyzed the expression, plasma membrane distribution and activity of the raft associative Src family kinase member Fyn, in scrapie-infected neuronal cell lines. As a result of prion infection, the specific tyrosine kinase activity of Fyn is increased, although the protein level of Fyn kinase is reduced. This results in an increased overall tyrosine phosphorylation in the infected cells. Interestingly, prion infection also induced a membrane redistribution of Fyn from non-raft to raft-membrane subdomains, following the distribution of PrPSc, as shown by immunoblotting of flotation-fractions after density gradient centrifugation of Triton X-100 extracted cell extracts. This indicates a persistent Fyn activation, possibly due to clustering of intracellular Fyn kinases as a result of PrPSc association to membrane rafts. An increased Fyn kinase activity followed by a dramatic increase in tyrosine phosphorylation may cause and/or contribute to synaptic disorganization and loss which are fundamental features of prion disease.
Creutzfelt-Jacobs disease, detergent resistant membranes, lipid rafts, GT1, RML
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject Neurochemistry and Neurotoxicology
IdentifiersURN: urn:nbn:se:su:diva-44380OAI: oai:DiVA.org:su-44380DiVA: diva2:369435