Journal
JOURNAL OF NEUROCHEMISTRY
Volume 110, Issue 3, Pages 912-923Publisher
WILEY
DOI: 10.1111/j.1471-4159.2009.06176.x
Keywords
bioaminergic autoreceptors; metalloproteinase; neuronal homeostasis; neurotransmitter metabolism; prion; tumor necrosis factor-alpha signaling
Categories
Funding
- Groupement d'Interet Scientifique-Infections Prions
- Agence Nationale pour la Recherche
- Fondation pour la Recherche Medicale
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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 (1C11(5-HT)) or noradrenergic (1C11(NE)) 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)-alpha release, through recruitement of the metalloproteinase TNF-alpha converting enzyme (TACE). TNF-alpha shed in response to PrPC acts as a second message signal, eliciting serotonin (5-HT) or norepinephrine (NE) degradation in 1C11(5-HT) or 1C11(NE) cells, respectively. Our data thus introduced TNF-alpha as a PrPC-dependent modulator of neuronal metabolism. Of note, we previously reported on a control of neurotransmitter catabolism by 5-HT2B or alpha(1D) autoreceptors in 1C11 bioaminergic neurons, via the same TACE/TNF-alpha 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.
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