Estudo Funcional de Mutantes da Proteína Prion Celular Associados à Doenças por Prion

STI1 used in the current experiments mimics the extracellular secreted STI1 and induced PrP C-mediated signal transduc- tion, as expected, for a neurotrophic factor.

It is well known that the association be- tween neurotrophic factors and cell- surface receptors induces diverse cellular signals. Some are triggered as the ligand binds to its cognate receptor at the cell sur- face, and others depend on the internaliza- tion of the receptor–ligand complex, a process known as endosomal signal trans- duction (Gonzalez-Gaitan, 2003). Indeed, evaluation of STI1 intracellular trafficking as well as its role on PrP C internalization is of particular interest to understand cell signaling associated with the neurotrophic functions mediated by PrP C–STI1 interac- tion. Previously, endocytosis of PrP C had been linked to a pro-apoptotic activity me- diated by p53 (Sunyach and Checler, 2005), but agonists that activate this pro- cess are unknown. Recently, it has been shown that signaling derived from STI1– PrP C interactions and associated with pro- liferation of glioblastoma cells depends on general cellular endocytic activity (Americo et al., 2007; Erlich et al., 2007). The present study identifies a mechanism by which PrP C is internalized and revealed that the endocytosis of PrP C is a determi- nant of STI1-induced cellular signaling. These observations raise the possibility that other events of PrP C-mediated signal- ing, such as those elicited by interaction with neural…