PRNP and infection: We provide evidence that (i) PrP conversion occurs within minutes after infection at two distinct cellular sites and precedes the formation of abnormal PrP conformers, (ii) fibril-like PrPd aggregates are formed and elongated at the plasma membrane, while PrPd fibrils are absent intracellularly, (iii) the prion infectious state is dependent on functional dynamins and Cdc42, (iv) PrPd segregates into synaptic and large-dense core vesicles of the regulated secretory pathway.