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Cellular prion protein coupling to TACE‐dependent TNF‐α shedding controls neurotransmitter catabolism in neuronal cells
Author(s) -
Pradines Elodie,
Loubet Damien,
MouilletRichard Sophie,
Manivet Philippe,
Launay JeanMarie,
Kellermann Odile,
Schneider Benoît
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06176.x
Subject(s) - neurotransmitter , coupling (piping) , catabolism , prion protein , microbiology and biotechnology , chemistry , neuroscience , biology , medicine , endocrinology , central nervous system , metabolism , disease , mechanical engineering , engineering
Despite considerable efforts to unravel the role of cellular prion protein (PrP C ) in neuronal functions, the mechanisms by which PrP C 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 PrP C to bioaminergic cell functions. We established that in 1C11‐derived neuronal cells antibody‐mediated PrP C ligation triggered tumor necrosis factor (TNF)‐α release, through recruitement of the metalloproteinase TNF‐α converting enzyme (TACE). TNF‐α shed in response to PrP C 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‐α as a PrP C ‐dependent modulator of neuronal metabolism. Of note, we previously reported on a control of neurotransmitter catabolism by 5‐HT 2B or α 1D 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 PrP C and these two bioaminergic receptors add their effects on neurotransmitter degradation. Overall, these observations unveil a novel contribution of PrP C to the control of neuronal functions and may have implications regarding dysfunction of the bioaminergic systems in prion diseases.