Prion protein inhibits fast axonal transport through a mechanism involving casein kinase 2
Caicedo, Hector Hugo
Jungbauer, Lisa M.
LaDu, Mary J.
Helguera, Pablo R.
Morfini, Gerardo A.
Brady, Scott T.
Pigino, Gustavo F.
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Prion diseases include a number of progressive neuropathies involving conformational changes in cellular prion protein (PrPc) that may be fatal sporadic, familial or infectious. Pathological evidence indicated that neurons affected in prion diseases follow a dying-back pattern of degeneration. However, specific cellular processes affected by PrPc that explain such a pattern have not yet been identified. Results from cell biological and pharmacological experiments in isolated squid axoplasm and primary cultured neurons reveal inhibition of fast axonal transport (FAT) as a novel toxic effect elicited by PrPc. Pharmacological, biochemical and cell biological experiments further indicate this toxic effect involves casein kinase 2 (CK2) activation, providing a molecular basis for the toxic effect of PrPc on FAT. CK2 was found to phosphorylate and inhibit light chain subunits of the major motor protein conventional kinesin. Collectively, these findings suggest CK2 as a novel therapeutic target to prevent the gradual loss of neuronal connectivity that characterizes prion diseases.
© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 12 (2017): e0188340, doi:10.1371/journal.pone.0188340.
Suggested CitationPLoS One 12 (2017): e0188340
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