It has been reported that cellular prion protein (PrPc) is enriched in caveolae or caveolae-like domains with caveolin-1 (Cav-1) participating to signal transduction events by Fyn kinase recruitment. By using the Glutathione-S-transferase (GST)-fusion proteins assay we observed that PrPc strongly interacts in vitro with Cav-1. Thus, we ascertained the PrPc caveolar localization in a hypothalamic neuronal cell line (GN11), by confocal microscopy analysis, flotation on density gradient and co-immunoprecipitation experiments. Following the anti-PrPc antibody-mediated stimulation of live GN11 cells, we observed that PrPc clustered on plasma membrane domains rich in Cav-1 in which Fyn kinase converged to be activated. After these events, a signaling cascade through p42/44 MAP kinase (Erk 1/2) was triggered, suggesting that following translocation from rafts to caveolae or caveolae-like domains PrPc could interact with Cav-1 and induce signal transduction events.

Cellular prion protein and Caveolin-1 interaction in a neuronal cell line precedes FYN / ERK1/2 signal transduction

TONI, MATTIA;SPISNI, ENZO;GRIFFONI, CRISTIANA;TOMASI, VITTORIO
2006

Abstract

It has been reported that cellular prion protein (PrPc) is enriched in caveolae or caveolae-like domains with caveolin-1 (Cav-1) participating to signal transduction events by Fyn kinase recruitment. By using the Glutathione-S-transferase (GST)-fusion proteins assay we observed that PrPc strongly interacts in vitro with Cav-1. Thus, we ascertained the PrPc caveolar localization in a hypothalamic neuronal cell line (GN11), by confocal microscopy analysis, flotation on density gradient and co-immunoprecipitation experiments. Following the anti-PrPc antibody-mediated stimulation of live GN11 cells, we observed that PrPc clustered on plasma membrane domains rich in Cav-1 in which Fyn kinase converged to be activated. After these events, a signaling cascade through p42/44 MAP kinase (Erk 1/2) was triggered, suggesting that following translocation from rafts to caveolae or caveolae-like domains PrPc could interact with Cav-1 and induce signal transduction events.
JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY
M.Toni; E.Spisni; C.Griffoni; S.Santi; M.Riccio; P.Lenaz; V. Tomasi
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/24217
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