Abstract
BackgroundIt has been reported that cellular prion protein (PrPc) co-localizes with caveolin-1 and participates to signal transduction events by recruiting Fyn kinase. As PrPc is a secreted protein anchored to the outer surface membrane through a glycosylphosphatidylinositol (GPI) anchor (secPrP) and caveolin-1 is located in the inner leaflet of plasma membrane, there is a problem of how the two proteins can physically interact each other and transduce signals.ResultsBy using the GST-fusion proteins system we observed that PrPc strongly interacts with caveolin-1 scaffolding domain and with a caveolin-1 hydrophilic C-terminal region, but not with the caveolin-1 N-terminal region. In vitro binding experiments were also performed to define the site(s) of PrPc interacting with cav-1. The results are consistent with a participation of PrPc octapeptide repeats motif in the binding to caveolin-1 scaffolding domain. The caveolar localization of PrPc was ascertained by co-immunoprecipitation, by co-localization after flotation in density gradients and by confocal microscopy analysis of PrPc and caveolin-1 distributions in a neuronal cell line (GN11) expressing caveolin-1 at high levels.ConclusionsWe observed that, after antibody-mediated cross-linking or copper treatment, PrPc was internalized probably into caveolae. We propose that following translocation from rafts to caveolae or caveolae-like domains, secPrP could interact with caveolin-1 and induce signal transduction events.
Highlights
It has been reported that cellular prion protein (PrPc) co-localizes with caveolin-1 and participates to signal transduction events by recruiting Fyn kinase
We propose that following translocation from rafts to caveolae or caveolae-like domains, secPrP could interact with caveolin-1 and induce signal transduction events
We have examined the role played by membrane microdomains in signal transduction generation using a hypothalamic neuronal cell line
Summary
It has been reported that cellular prion protein (PrPc) co-localizes with caveolin-1 and participates to signal transduction events by recruiting Fyn kinase. Signal transduction in neurons is used mainly to trigger cell survival and differentiation , but much less is known about the constituents participating to the transduction cascade especially as far as protein kinase family members acting downstream are concerned [1]. MAP kinase (ERK1/2) has been intensively studied in neurons because of its participation to hippocampal mechanisms leading to learning and memory consolidation [2]. How this kinase is recruited by signalosomes is. A member of src family kinase, unlike ERK1/2 has clearly been shown to be recruited in membrane microdomains and to interact there with ephrin A. Davy et al interestingly proposed that a transmembrane adaptor may be involved in coupling ephrin A activation to signal transduction Fyn kinase-mediated [5]
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