TY - GEN
T1 - Cellular prion protein signaling in serotonergic neuronal cells
AU - Mouillet-Richard, Sophie
AU - Schneider, Benoît
AU - Pradines, Elodie
AU - Pietri, Mathéa
AU - Ermonval, Myriam
AU - Grassi, Jacques
AU - Richards, J. Grayson
AU - Mutel, Vincent
AU - Launay, Jean Marie
AU - Kellermann, Odile
PY - 2007/1/1
Y1 - 2007/1/1
N2 - The cellular prion protein PrPC is the normal counterpart of the scrapie prion protein PrPSc, the main component of the infectious agent of transmissible spongiform encephalopathies (TSEs). It is a ubiquitous cell-surface glycoprotein, abundantly expressed in neurons, which constitute the targets of TSE pathogenesis. Taking advantage of the 1C11 neuroectodermal cell line, endowed with the capacity to convert into 1C115-HT serotonergic or 1C11NE noradrenergic neuronal cells, allowed us to ascribe a signaling function to PrPC. Antibody-mediated ligation of PrP C recruits transduction pathways, which involve nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent reactive oxygen species production and target the extracellular-regulated kinases ERK1/2. In fully differentiated cells only, these effectors are under the control of a PrP C-caveolin-Fyn platform, located on neuritic extensions. In addition to its proper signaling activity, PrPC modulates the agonist-induced response of the three serotonergic G protein-coupled receptors present on the 1C115-HT differentiated cells. The impact of PrPC ligation on the receptor couplings depends on the receptor subtype and the pathway considered. The implementation of the PrPC-caveolin complex again is mandatory for PrPC to exert its action on 5-HT receptor signaling. Our current data argue that PrPC interferes with the intensities and/or dynamics of G protein activation by agonist-bound 5-HT receptors. By mobilizing transduction cascades controlling the cellular redox state and the ERK1/2 kinases and by altering 5-HT receptor-mediated intracellular response, PrPC takes part in the homeostasis of serotonergic neuronal cells. These findings may have implications for future research aiming at understanding the fate of serotonergic neurons in prion diseases.
AB - The cellular prion protein PrPC is the normal counterpart of the scrapie prion protein PrPSc, the main component of the infectious agent of transmissible spongiform encephalopathies (TSEs). It is a ubiquitous cell-surface glycoprotein, abundantly expressed in neurons, which constitute the targets of TSE pathogenesis. Taking advantage of the 1C11 neuroectodermal cell line, endowed with the capacity to convert into 1C115-HT serotonergic or 1C11NE noradrenergic neuronal cells, allowed us to ascribe a signaling function to PrPC. Antibody-mediated ligation of PrP C recruits transduction pathways, which involve nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent reactive oxygen species production and target the extracellular-regulated kinases ERK1/2. In fully differentiated cells only, these effectors are under the control of a PrP C-caveolin-Fyn platform, located on neuritic extensions. In addition to its proper signaling activity, PrPC modulates the agonist-induced response of the three serotonergic G protein-coupled receptors present on the 1C115-HT differentiated cells. The impact of PrPC ligation on the receptor couplings depends on the receptor subtype and the pathway considered. The implementation of the PrPC-caveolin complex again is mandatory for PrPC to exert its action on 5-HT receptor signaling. Our current data argue that PrPC interferes with the intensities and/or dynamics of G protein activation by agonist-bound 5-HT receptors. By mobilizing transduction cascades controlling the cellular redox state and the ERK1/2 kinases and by altering 5-HT receptor-mediated intracellular response, PrPC takes part in the homeostasis of serotonergic neuronal cells. These findings may have implications for future research aiming at understanding the fate of serotonergic neurons in prion diseases.
KW - Caveolin
KW - GPCR
KW - Prion protein
KW - Serotonergic neurons
U2 - 10.1196/annals.1397.076
DO - 10.1196/annals.1397.076
M3 - Conference contribution
C2 - 17405922
AN - SCOPUS:34247185369
SN - 1573316970
SN - 9781573316972
T3 - Annals of the New York Academy of Sciences
SP - 106
EP - 119
BT - Signal Transduction Pathways, Part D
PB - Blackwell Publishing Inc.
ER -