Prions prefer caveosomes

The story of prions gets increasingly bizarre. The peculiar pathogenicity of prion protein (PrP) makes understanding and treating the resulting diseases difficult. Now, on page 703, Peters et al. provide evidence that PrP also uses an unusual endocytic pathway en route to lysosomes.The harmless version of PrP is processed and directed to caveolin-rich glycolipid rafts at the plasma membrane, although its function remains a mystery. The misfolded pathogenic form, however, is found in late endosomes and lysosomes. The group now shows that, unlike most internalized proteins, which use the typical clathrin-dependent endocytosis pathway, PrP finds its way to lysosomes through an endosomal compartment that lacks clathrin but contains caveolin-1.

The results contrast another study that reported colocalization of PrP and clathrin in vesicles. But the cryoimmunogold EM method used by Peters...