![]() ![]() ![]() Cargo proteins localized to endosomes follow several distinct trafficking pathways: including the ubiquitin-mediated degradation pathway to the lysosome the retrograde pathway to the Golgi and the recycling pathway back to the plasma membrane. ![]() Internalized cell surface membrane proteins move to a common, early endosome. Additionally, specialized signals have been described that allow efficient transit along early endosome-to-PM recycling routes. Even from recycling endosomes, cargo may be segregated into different pathways despite this plethora of sub-pathways, the general ability of proteins to recycle back to the PM is thought to reflect a ‘default’ pathway, since proteins without any known trafficking signals can be conveyed back to the PM after internalizing. Alternatively, proteins travel to recycling endosomes marked by Rab11, and then return to the PM via tubulovesicular structures controlled by a number of known proteins such as Rab11, its effectors, and Eps15 homology domain (EHD) proteins. Proteins returning to the PM can transit via a direct, fast recycling route that remains poorly defined at the mechanistic level. Here, proteins internalized by a variety of routes converge in early sorting endosomes, defined by a mildly acidic pH and markers such as Rab5 and EEA1. Studies from cultured mammalian cells revealed a general itinerary for proteins that travel through the endocytic pathway. Early work following the internalization kinetics of receptors revealed that membrane turnover at the surface was constantly in flow from endosomes and that receptors used this process to repopulate the surface following ligand-uncoupling. In addition to sorting lipids and soluble molecules, endosomes parse internalized integral membrane proteins into different pathways to either effect their lysosomal degradation or their return to the plasma membrane (PM), trans-Golgi network (TGN), or other compartments within the endomembrane system ( Figure 1). The process of endocytosis involves packaging of cell surface material into vesicles that are internalized and incorporated into the endosomal system, a complex network that intersects various intracellular trafficking pathways. ![]()
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