A PrPC-caveolin-Lyn complex negatively controls neuronal GSK3β and serotonin 1B receptor

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 re...

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Veröffentlicht in:Scientific reports 2014-05, Vol.4 (1), Article 4881
Hauptverfasser: Hernandez-Rapp, Julia, Martin-Lannerée, Séverine, Hirsch, Théo Z., Pradines, Elodie, Alleaume-Butaux, Aurélie, Schneider, Benoît, Baudry, Anne, Launay, Jean-Marie, Mouillet-Richard, Sophie
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Sprache:eng
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Zusammenfassung: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-HT 1B R), 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-HT 1B R activity, whose inhibition promotes an anxiogenic behavioural response. Collectively, our data unveil a new facet of PrP C signalling that strengthens neurotransmission.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep04881