The endocytic pathway: a mosaic of domains

In the endocytic pathway, internalized molecules are delivered to early endosomes, where efficient sorting occurs. Although some molecules, in particular recycling receptors, are rapidly recycled back to the plasma membrane for reutilization; others, including downregulated receptors, are transported to late endosomes and lysosomes for degradation. Early endosomes exhibit a highly pleiomorphic organization, and transport intermediates formed on early endosomal membranes — along recycling and degradation routes — also differ significantly both morphologically and functionally. Selective changes must occur in bilayer organization during biogenesis of these intermediates, and these changes might contribute to protein sorting. Although recycling occurs through thin tubules, transport to late endosomes is mediated by multivesicular intermediates (endosomal carrier vesicles/multivesicular bodies; ECV/MVBs). In addition to this morphologically visible mosaic of membrane domains, key components that regulate membrane organization and protein transport are also distributed in a non-random manner on endosomal membranes. Late endosomes also exhibit a highly pleiomorphic organization, including numerous membrane invaginations with a specific lipid composition. These invaginations seem to have a role not only in cargo degradation, but also in protein–lipid transport through the compartment. Candidate proteins and lipids that regulate the dynamics of these invaginations have been identified. Lysosomes can only be identified at the molecular level by the fact that they lack a few proteins found in late endosomes. Both compartments might represent separate elements of a common dynamic network, involved in sorting and degradation, respectively. Membrane invaginations might have turnpike functions in the network, as they seem to be involved in both transport and degradation. Since a given combination of protein–lipid machines and regulatory factors — but not individual components — seem unique to each endocytic compartment and are distributed non-randomly on membranes, it is attractive to speculate that endosomal membranes are built from modular elements.