Prion receptors, prion internalization, intra- and inter-cellular transport


Progress in Molecular Biology and Translational Science


20 February, 2023


Luigi Celauro, Marco Zattoni, Giuseppe Legname

Cellular prion protein (PrPC) is a membrane bound protein that undergoes several post translational modifications. It can exert pleiotropic functions either in physiological and pathological conditions. The disease-causing isoform of the prion protein, called PrPSc, acts as corruptive seed able to establish a process of misfolding and aggregation of further PrPSc molecules. Therefore, PrPC acts as substrate for PrPSc formation and as receptor to convey neurotoxic functions typical of other prion-like proteins involved in several neurodegenerative conditions.

PrPC is transported from the outer leaflet of the cellular membrane to the intracellular compartments through several endocytic pathways, including clathrin-dependent and independent mechanisms and interactions with different adaptor proteins. During prion infection, the pathological counterpart PrPSc, can be uptaken by the cells with mechanisms partially overlapping the ones of the physiological form, PrPC.

The intercellular routing of both prion protein isoforms involves the release through vesicles and tunneling nanotubes. From the extracellular milieu, PrPC and PrPSc can be uptaken by adjacent cells, thus exerting physiological and pathological functions.