TY - JOUR
T1 - Cellular prion protein coupling to TACE-dependent TNF-α shedding controls neurotransmitter catabolism in neuronal cells
AU - Pradines, Elodie
AU - Loubet, Damien
AU - Mouillet-Richard, Sophie
AU - Manivet, Philippe
AU - Launay, Jean Marie
AU - Kellermann, Odile
AU - Schneider, Benoît
PY - 2009/8/1
Y1 - 2009/8/1
N2 - Despite considerable efforts to unravel the role of cellular prion protein (PrPC) in neuronal functions, the mechanisms by which PrPC takes part in the homeostasis of a defined neuronal phenotype remain poorly characterized. By taking advantage of a neuroectodermal cell line (1C11) endowed with the capacity to differentiate into serotonergic (1C115-HT) or noradrenergic (1C11NE) neurons, we assessed the contribution of PrPC to bioaminergic cell functions. We established that in 1C11-derived neuronal cells antibody-mediated PrPC ligation triggered tumor necrosis factor (TNF)-α release, through recruitement of the metalloproteinase TNF-α converting enzyme (TACE). TNF-α shed in response to PrPC acts as a second message signal, eliciting serotonin (5-HT) or norepinephrine (NE) degradation in 1C115-HT or 1C11 NE cells, respectively. Our data thus introduced TNF-α as a PrPC-dependent modulator of neuronal metabolism. Of note, we previously reported on a control of neurotransmitter catabolism by 5-HT 2B or α1D autoreceptors in 1C11 bioaminergic neurons, via the same TACE/TNF-α pathway (Ann. N Y Acad. Sci. 1091, 123). Here, we show that combined stimulation of PrPC and these two bioaminergic receptors add their effects on neurotransmitter degradation. Overall, these observations unveil a novel contribution of PrPC to the control of neuronal functions and may have implications regarding dysfunction of the bioaminergic systems in prion diseases.
AB - Despite considerable efforts to unravel the role of cellular prion protein (PrPC) in neuronal functions, the mechanisms by which PrPC takes part in the homeostasis of a defined neuronal phenotype remain poorly characterized. By taking advantage of a neuroectodermal cell line (1C11) endowed with the capacity to differentiate into serotonergic (1C115-HT) or noradrenergic (1C11NE) neurons, we assessed the contribution of PrPC to bioaminergic cell functions. We established that in 1C11-derived neuronal cells antibody-mediated PrPC ligation triggered tumor necrosis factor (TNF)-α release, through recruitement of the metalloproteinase TNF-α converting enzyme (TACE). TNF-α shed in response to PrPC acts as a second message signal, eliciting serotonin (5-HT) or norepinephrine (NE) degradation in 1C115-HT or 1C11 NE cells, respectively. Our data thus introduced TNF-α as a PrPC-dependent modulator of neuronal metabolism. Of note, we previously reported on a control of neurotransmitter catabolism by 5-HT 2B or α1D autoreceptors in 1C11 bioaminergic neurons, via the same TACE/TNF-α pathway (Ann. N Y Acad. Sci. 1091, 123). Here, we show that combined stimulation of PrPC and these two bioaminergic receptors add their effects on neurotransmitter degradation. Overall, these observations unveil a novel contribution of PrPC to the control of neuronal functions and may have implications regarding dysfunction of the bioaminergic systems in prion diseases.
KW - Bioaminergic autoreceptors
KW - Metalloproteinase
KW - Neuronal homeostasis
KW - Neurotransmitter metabolism
KW - Prion
KW - Tumor necrosis factor-α signaling
U2 - 10.1111/j.1471-4159.2009.06176.x
DO - 10.1111/j.1471-4159.2009.06176.x
M3 - Article
C2 - 19457070
AN - SCOPUS:67650459027
SN - 0022-3042
VL - 110
SP - 912
EP - 923
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 3
ER -