The prion protein and its paralogue doppel affect calcium signaling in chinese hamster ovary cells

摘要

The function of the prion protein (PrPc), implicated in transmissible spongiform. encephalopathies (TSEs), is largely unknown. We examined the possible influence of PrPc on Ca2+ homeostasis, by analyzing local Ca2+ fluctuations in cells transfected with PrPc and Ca2+-sensitive aequorin chimeras targeted to defined subcellular compartments. In agonist-stimulated cells' the presence of PrPc sharply increases the Ca2+ concentration of subplasma membrane Ca2+ domains, a feature that may explain the impairment of Ca2+-dependent neuronal excitability observed in TSEs. PrPc also limits Ca2+ release from the endoplasmic reticulum and Ca2+ uptake by mitochondria, thus rendering unlikely the triggering of cell death pathways. Instead, cells expressing Doppel, a PrPc paralogue, display opposite effects, which, however, are abolished by the coexpression of PrPc. These findings are consistent with the functional interplay and antagonistic role attributed to the proteins, whereby PrPc protects, and Doppel sensitizes, cells toward stress conditions.