The prion protein family member Shadoo induces spontaneous ionic currents in cultured cells

Antal Nyeste, Claudia Stincardini, Petra Bencsura, Milica Cerovic, Emiliano Biasini, E. Welker

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Abstract

Some mutant forms of the cellular prion protein (PrP C) carrying artificial deletions or point mutations associated with familial human prion diseases are capable of inducing spontaneous ionic currents across the cell membrane, conferring hypersensitivity to certain antibiotics to a wide range of cultured cells and primary cerebellar granular neurons (CGNs). These effects are abrogated when the wild type (WT) form is co-expressed, suggesting that they might be related to a physiological activity of PrP C. Interestingly, the prion protein family member Shadoo (Sho) makes cells hypersensitive to the same antibiotics as mutant PrP-s, an effect that is diminished by the co-expression of WT-PrP. Here, we report that Sho engages in another mutant PrP-like activity: it spontaneously induces large ionic currents in cultured SH-SY5Y cells, as detected by whole-cell patch clamping. These currents are also decreased by the co-expression of WT-PrP. Furthermore, deletion of the N-terminal (RXXX) 8 motif of Sho, mutation of the eight arginine residues of this motif to glutamines, or replacement of the hydrophobic domain by that of PrP, also diminish Sho-induced ionic currents. Our results suggest that the channel activity that is also characteristic to some pathogenic PrP mutants may be linked to a physiological function of Sho.

Original languageEnglish
Article number36441
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Nov 7 2016

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Cultured Cells
Anti-Bacterial Agents
Prion Diseases
Sequence Deletion
Protein C
Glutamine
Point Mutation
Constriction
Arginine
Hypersensitivity
Cell Membrane
Neurons
Mutation
Prion Proteins

ASJC Scopus subject areas

  • General

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The prion protein family member Shadoo induces spontaneous ionic currents in cultured cells. / Nyeste, Antal; Stincardini, Claudia; Bencsura, Petra; Cerovic, Milica; Biasini, Emiliano; Welker, E.

In: Scientific Reports, Vol. 6, 36441, 07.11.2016.

Research output: Contribution to journalArticle

Nyeste, Antal ; Stincardini, Claudia ; Bencsura, Petra ; Cerovic, Milica ; Biasini, Emiliano ; Welker, E. / The prion protein family member Shadoo induces spontaneous ionic currents in cultured cells. In: Scientific Reports. 2016 ; Vol. 6.
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AU - Welker, E.

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