Fig. 1.

Endosomal pathways. a Overview of the major endosomal pathways in mammalian cells. The plasma membrane with protein cargo is endocytosed and forms intracellular endocytic vesicles (EV). Those vesicles homotypically fuse with each other and subsequently fuse with early endosomes (EE). EE are major sorting compartments within the cell. Endocytosed material is sorted into tubular structures and bud off as recycling endosomes (RE) which migrate back to the plasma membrane and exocytose there. Moreover, a process starts in early endosomes which results in the formation of endosomal carrier vesicles (yellow). During retro- and anterograde connections to the trans-Golgi endosomal cargo, newly formed proteins are exchanged. By an ongoing production of endosomal carrier vesicles and RE, the EE changes its shape and molecular composition and becomes a late endosome (LE). Finally late endosomes fuse with lysosomes (Lys) in which the remaining cargo mainly localized in endosomal carrier vesicles (multivesicular body) is degraded by hydrolytic enzymes. In some cell types such as cytotoxic T lymphocytes, LE can produce lysosomal-related organelles (LRO) that, as secretory lysosomes, become released by regulated exocytosis. Specific cargo may be inserted into LRO via a transport pathway from trans-Golgi via LE to LRO. b Closeup of EE and LE with some important molecular components; early endosomal antigen 1 (EEA1), endosomal sorting complexes required for transport (ESCRT), small GTPases (Rab5, Rab7, Rab11), sorting nexin (SNX)