Data from: Prion protein inhibits fast axonal transport through a mechanism involving casein kinase 2

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.