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

somes (58). The group I mGluRs are also located in lipid rafts, and the interaction with caveolin 1 modu- lates their internalization (59). Thus, it is possible that PrPC and mGluR1/5 interact when they colocalize in the same raft domain, although this remains to be established. The Ln `)`1 peptide binding to PrPC may change the conformation of PrPC similarly to what is described on hop/STI1 binding to PrPC (60). Future experiments aimed at understanding  these  mecha- nisms may clarify novel roles of PrPC in glutamate signaling.

Group I mGluRs have been implicated in the target- ing of thalamic axons to somatosensory cortical barrels

(61) and are found to promote dendritic protein synthesis (62). The activation of mGluR1 decreases the proliferation and increases differentiation of early neu- ronal progenitors, whereas mGluR5 promotes the sur- vival of neuronal-restricted precursors (63), indicating that group I mGluRs control neuronal  differentiation and are important for brain development. Our data are in line with these observations, in that we showed that activation of either mGluR1 or GluR5 increases neuri- togenesis. Moreover, the blockade of either mGluR1 or mGluR5 inhibits PrPC-Ln `)`1 peptide-induced neurito- genesis.

The characterization of group I mGluRs as trans- membrane proteins connecting  PrPC-Ln  engagement to neuronal plasticity, provide a cellular mechanism by which PrPC can transduce extracellular signals. These results further support…