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

ZAMPONI EMILIANO; BURRATTI FIAMMA; CATALDI GABRIEL; CAICEDO HECTOR H; SONG YUYU; JUNGBAUER LISA; LADU MARY J; BISBAL MARIANO ; LORENZO ALFREDO; MA JIYAN; HELGUERA PABLO; MORFINI GERARDO; BRADY SCOTT; PIGINO GUSTAVO F

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2017

1932-6203

Prion diseases include a number of progressive neuropathies involving conformationalchanges 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-backpattern of degeneration. However, specific cellular processes affected by PrPc that explainsuch a pattern have not yet been identified. Results from cell biological and pharmacologicalexperiments in isolated squid axoplasm and primary cultured neurons reveal inhibition offast axonal transport (FAT) as a novel toxic effect elicited by PrPc. Pharmacological, biochemical and cell biological experiments further indicate this toxic effect involves caseinkinase 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 proteinconventional kinesin. Collectively, these findings suggest CK2 as a novel therapeutic targetto prevent the gradual loss of neuronal connectivity that characterizes prion diseases.