Laminin‐induced PC‐12 cell differentiation is inhibited following laser inactivation of cellular prion protein

Abstract

Prions, the etiological agents for infectious degenerative encephalopathies, act by inducing structural modifications in the cellular prion protein (PrPc). Recently, we demonstrated that PrPc binds laminin (LN) and that this interaction is important for the neuritogenesis of cultured hippocampal neurons. Here we have used the PC-12 cell model to explore the biological role of LN^PrPc interaction. Antibodies against PrPc inhibit cell adhesion to LN-coated culture plaques. Furthermore, chromophore-assisted laser inactivation of cell surface PrPc perturbs LN-induced differentiation and promotes retraction of mature neurites. These results point out to the importance of PrPc as a cell surface ligand for LN. ß

PrPc is temporospatially expressed in molar development of rats

“…PrP c has high affinity to laminin with a binding domain to mediate neurite formation and neuronal cell adhesion (Liesi et al, 1989;Graner et al, 2000a). Neurite extension elicited by laminin was inhibited by an anti-prion protein (Graner et al, 2000b). In this study, PrP c was localized in nerve fibers in the dental papilla of the second molar germs, the presence of which was also demonstrated by silver stain.…”

Prion protein ablation increases cellular aggregation and embolization contributing to mechanisms of metastasis

“…2 The association of PrP C and STI1 mediates neuronal survival and differentiation, 8 similarly the association of PrP C with laminin (LN) and vitronectin (VN) promotes neuronal adhesion and differentiation. [9][10][11] Since PrP C functions are very broad, we hypothesize that alterations in PrP C expression and/or activity are associated with pathological conditions. For instance, PrP C partners, such as those described above, are involved in the control of cellular adhesion, programmed cell death and differentiation.…”

“…The embolization of tumor cells with platelets and other circulating blood cells greatly facilitates their aggregation and retention in the lung vasculature. [32][33][34][35] Since PrP C has been shown to modulate cell adhesion, 9,10 we investigated the role of PrP C in cellular aggregation/embolization in the presence of blood components. Clones V12 (Prnp 1/1 ras/myc) and C5 (Prnp 0/0 ras/myc) were mixed with whole blood and plated onto collagen-coated coverslips, an in vitro model of a thrombogenic matrix.…”

Fonctions de la protéine prion PrPc

“…De plus, il est intéressant de noter que la PrP c peut également lier directement la laminine et que cette interaction s'est révélée essentielle à la formation de neurites par des neurones d'hippocampe en culture primaire [20]. Inversement, l'inactivation de la PrP c dans la lignée PC12 entraîne une inhibition de la différenciation cellulaire dépendante de la laminine et une rétraction des neurites [21]. Des études plus récentes indiquent que l'interaction de la PrP c avec NCAM serait aussi impliquée dans la neuritogenèse : cette réponse implique le recrutement de NCAM par la PrP c au niveau des radeaux lipidiques et l'activation de la protéine kinase Fyn [22].…”