NR ATSQ
AU Brini,M.; Miuzzo,M.; Pierobon,N.; Negro,A.; Sorgato,M.C.
TI The prion protein and its paralogue Doppel affect calcium signaling in Chinese hamster ovary cells
QU Molecular Biology of the Cell 2005 Jun; 16(6): 2799-808
IA http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1142425
PT journal article
AB The function of the prion protein (PrPc), implicated in transmissible spongiform encephalopathies (TSEs), is largely unknown. We examined the possible influence of PrPc on Ca(2+) homeostasis, by analyzing local Ca(2+) fluctuations in cells transfected with PrPc and Ca(2+)-sensitive aequorin chimeras targeted to defined subcellular compartments. In agonist-stimulated cells, the presence of PrPc sharply increases the Ca(2+) concentration of subplasma membrane Ca(2+) domains, a feature that may explain the impairment of Ca(2+)-dependent neuronal excitability observed in TSEs. PrPc also limits Ca(2+) release from the endoplasmic reticulum and Ca(2+) 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.
MH Adenosine Triphosphate/pharmacology; Animals; Antibodies, Monoclonal/metabolism; Blotting, Western; CHO Cells; Calcium/metabolism; Calcium Signaling/*drug effects; Cell Culture Techniques; Cell Membrane/drug effects/metabolism; Chelating Agents/pharmacology; Comparative Study; Cricetinae; Cricetulus; Cytosol/chemistry; Densitometry; Endoplasmic Reticulum/drug effects/secretion; Fura-2/pharmacology; Green Fluorescent Proteins/metabolism; Homeostasis; Immunohistochemistry; Mitochondria/drug effects/metabolism; PrPc Proteins/genetics/*pharmacology; Prions/genetics/*pharmacology; Recombinant Proteins/pharmacology; Research Support, Non-U.S. Gov't
AD Marisa Brini, Manuela Miuzzo, Nicola Pierobon, Maria Catia Sorgato (catia.sorgato@unipd.it), Department of Biological Chemistry, University of Padova, CNR Institute of Neuroscience and CRIBI, 35121 Padova, Italy; Alessandro Negro, Department of Experimental Veterinary Sciences, University of Padova, 35020 Legnaro-Padova, Italy
SP englisch
PO USA