Cellular Prion Protein and Caveolin‐1 Interaction in a Neuronal Cell Line Precedes Fyn/Erk 1/2 Signal Transduction

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 coimmunoprecipitation 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 translocations from rafts to caveolae or caveolaelike domains PrPc could interact with Cav-1 and induce signal transduction events.

K Ca 3.1 upregulation preserves endothelium‐dependent vasorelaxation during aging and oxidative stress

“…4A). As H 2 O 2 (Choi et al ., 2013b) and Fyn (Toni et al ., 2006) play critical roles in extracellular signal‐regulated kinase (ERK) activation, we examined phosphorylated ERK (p‐ERK) levels in MAECs. In aged wild‐type and young CerS2 null MAECs, p‐ERK levels were increased (Fig.…”

“…Consistent with these results, H 2 O 2 increased the phosphorylation of the Src family kinase Fyn. H 2 O 2 and Fyn play critical roles in ERK activation (Toni et al ., 2006; Choi et al ., 2013b). As K Ca 3.1 synthesis occurs via an ERK/activator protein‐1‐mediated pathway, K Ca 3.1 synthesis might be induced via a H 2 O 2 /Fyn/ERK‐mediated pathway.…”

Alzheimer's Disease and Prion Protein

“…PrP C is an extracellular protein attached to the outer surface of the cell membrane by a GPI anchor, and Fyn is located in the cytoplasm. Current evidence indicates that factors like caveolin-1 or the neural cell adhesion molecule (NCAM) could potentially connect PrP C and Fyn from the two opposite sides of the cell membrane (48,(67)(68)(69).…”

Misfolding of the prion protein: linking biophysical and biological approaches

“…The recent studies of PrP interactions seem to point towards interactions of PrP with extracellular proteins such as vitronectin [44] or glycosaminoglycans (heparin) and with proteins located in rafts like caveolin-1 [127] to transduct signals via the Fyn pathway. These signals could induce neuroprotection or neuritogenesis [61] or even short term and longterm memory [22].…”