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Sci Rep. 2014 May 8;4:4881. doi: 10.1038/srep04881.

A PrP(C)-caveolin-Lyn complex negatively controls neuronal GSK3β and serotonin 1B receptor.

Author information

1
1] INSERM UMR-S1124, 75006 Paris France [2] Université Paris Descartes, Sorbonne Paris Cité, UMR-S1124, 75006 Paris France [3] Université Paris Sud 11, ED419 Biosigne, 91400 Orsay, France [4].
2
1] INSERM UMR-S1124, 75006 Paris France [2] Université Paris Descartes, Sorbonne Paris Cité, UMR-S1124, 75006 Paris France [3].
3
1] INSERM UMR-S1124, 75006 Paris France [2] Université Paris Descartes, Sorbonne Paris Cité, UMR-S1124, 75006 Paris France.
4
1] AP-HP Service de Biochimie, Fondation FondaMental, INSERM U942 Hôpital Lariboisière, 75010 Paris, France [2] Pharma Research Department, F. Hoffmann-La-Roche Ltd., CH-4070 Basel, Switzerland.

Abstract

The cellular prion protein, PrP(C), is a glycosylphosphatidylinositol-anchored protein, abundant in lipid rafts and highly expressed in the brain. While PrP(C) is much studied for its involvement under its abnormal PrP(Sc) isoform in Transmissible Spongiform Encephalopathies, its physiological role remains unclear. Here, we report that GSK3β, a multifunctional kinase whose inhibition is neuroprotective, is a downstream target of PrP(C) signalling in serotonergic neuronal cells. We show that the PrP(C)-dependent inactivation of GSK3β is relayed by a caveolin-Lyn platform located on neuronal cell bodies. Furthermore, the coupling of PrP(C) to GSK3β potentiates serotonergic signalling by altering the distribution and activity of the serotonin 1B receptor (5-HT1BR), a receptor that limits neurotransmitter release. In vivo, our data reveal an increased GSK3β kinase activity in PrP-deficient mouse brain, as well as sustained 5-HT1BR activity, whose inhibition promotes an anxiogenic behavioural response. Collectively, our data unveil a new facet of PrP(C) signalling that strengthens neurotransmission.

PMID:
24810941
PMCID:
PMC4013941
DOI:
10.1038/srep04881
[Indexed for MEDLINE]
Free PMC Article

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