Prions and retroviruses: an endosomal rendezvous?

Abstract

The past two decades have seen the emergence of endocytic pathways as highly regulated systems for the sorting, selective degradation and recycling of nearly all cell‐surface membrane proteins. At the centre of these pathways are complex endosomal structures known as multivesicular bodies (MVBs) that house intraluminal vesicles (ILVs) formed by invagination and budding from the limiting membrane (Fig 1A). The ILVs contain membrane proteins from the Golgi complex and cell surface that are destined typically for degradation after the fusion of MVBs with lysosomes. This constitutive fate of ILVs is universal to eukaryotes and represents one of the main pathways for membrane protein degradation (Katzmann et al , 2002). Figure 1. Protein transport in the endo‐lysosomal pathways. ( A ) Topological relationships of the multivesicular body (MVB). Different types of cell‐surface proteins (indicated by blue and red molecules) can be internalized and transported by various routes (arrows) to endosomal compartments. The endosomal compartment is known as an MVB when its lumen contains intraluminal vesicles (ILVs) that are formed by budding from the limiting membrane. If the MVB fuses with the plasma membrane, ILVs are released into the extracellular space and become known as exosomes. ( B ) Transport into and out of the multivesicular body (MVB). Pathways linking the MVB with other compartments, such as the early endosome (EE), Golgi, lysosome and plasma membrane, are all regulated in a substrate‐specific and cell‐type‐specific manner to control the localization and fate of various membrane proteins (blue, red and green molecules). Alterations of these transport pathways is emerging as a key facet of viral pathogenesis and might also influence the intracellular accumulation and cell‐to‐cell transmission of prions. For example, adjacent cells, through interactions among cell surface signalling or adhesion molecules, might stimulate localized MVB fusion with the plasma membrane to facilitate exosome release and intercellular transfer of their cargo. …