Stop and go L1CAM

Prions prefer caveosomes he 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 mis-folded pathogenic form, however, is found T PrP (small gold particles) is found in endocytic structures with caveolin-1 (large particles). 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 et al. allows for higher resolution of the vesicles and their contents. Simian virus 40 particles were also shown to be taken in through caveolin-containing, clathrin-negative structures that are connected to an endocytic vacuole (collectively termed caveosomes). Although the PrP-containing Stop and go L1CAM mobile adhesion receptor allows a cell to migrate, whereas a stationary version of the same receptor keeps it in place, based on results from Gil et al. on page 719. The immunoglobulin family member L1CAM promotes both growth cone extension in the developing central nervous system and cell adhesion-mediated maintenance of axon bundles in mature neurons. How the same adhesion molecule regulates these disparate functions is not clear, particularly since the L1 family does not undergo the class switching (from adhesion-promoter to migration-promoter) that seems to be common in integrins. Rather than changing receptor types, L1CAM switches its own kinetic behavior to modulate cell movements. Stationary L1CAM, which may be associated with adhesion, was found to depend on ankyrin to stay in place. A vesicles lacked virus, the two atypical endocytic structures may be one and the same. If so, this EM study is the first ultrastructural view of caveosomes, which contain raft domains that are preferred by membrane-bound PrP. Both the low pH and high concentration of raft lipids in the caveolin-containing compartment may favor PrP conversion to the pathogenic form. Therefore, the group expects that caveolin knockout mice should be less susceptible to oral prions, but they await use of these mice to test their …