FIGURE 2.17 • Schematic diagram of endosomal compartments of the cell. This diagram shows the fate of protein (red circles) endocytosed from the cell surface and destined for lysosomal destruction. Proteins are frst found in endocytotic (coated) vesicles that deliver them to early endosomes, which are located in the peripheral part of cytoplasm. Because of the sorting capability of the early endosomes, receptors are usually recycled to the plasma membrane, and endocytosed proteins are transported via multi-vesicular bodies (MVB) to late endosomes positioned near the Golgi apparatus and the nucleus. The proteins transported to late endosomes eventually will be degraded in lysosomes. Note the acidifcation scale (left) that illustrates changes of pH from early endosomes to lysosomes. The acidifcation is accomplished by the active transport of protons into endosomal compartments.
Early endosomes sort proteins that have been internalized by endocytotic processes. The morphologic shape and geometry of the tubules and vesicles emerging from the early endosome create an environment in which localized changes in pH constitute the basis of the sorting mechanism. This mechanism includes dissociation of ligands from their receptor protein; thus, in the past, early endosomes were referred to as compartments of uncoupling receptors and ligands (CURLs). In addition, the narrow diameter of the tubules and vesicles may also aid in the sorting of large molecules, which can be mechanically prevented from entering specific sorting compartments. After sorting, most of the protein is rapidly recycled, and the excess membrane is returned to the plasma membrane.
The fate of the internalized ligand–receptor complex depends on the sorting and recycling ability of the early endosome.
The following pathways for processing internalized ligand–receptor complexes are present in the cell:  The receptor is recycled and the ligand is degraded. Surface receptors allow the cell to bring in substances selectively through the process of endocytosis. This pathway occurs most often in the cell; it is important because it allows surface receptors to be recycled. Most ligand–receptor complexes dissociate in the acidic pH of the early endosome. The receptor, most likely an integral membrane protein (see page 29), is recycled to the surface via vesicles that bud off the ends of narrow-diameter tubules of the early endosome. Ligands are usually  sequestered in the spherical vacuolar part of the  endosome that will later form MVBs, which will transport the ligand to late endosomes for further degradation in the lysosome (Fig. 2.18a). This pathway is described for the low-density lipoprotein (LDL)–receptor complex, insulin–glucose transporter (GLUT) receptor  complex, and a variety of peptide hormones and their receptors.
 Both receptor and ligand are recycled. Ligand–receptor complex dissociation does not always accompany receptor recycling. For example, the low pH of the endosome dissociates iron from the iron-carrier protein transferrin, but transferrin remains associated with its receptor. Once the transferrin–receptor complex returns to the cell surface, however, transferrin is released. At neutral extracellular pH, transferrin must again bind iron to be recognized by and bound to its receptor. A similar pathway is  recognized for major histocompatibility complex (MHC) I and II molecules, which are recycled to the cell surface with a foreign antigen protein attached to them (Fig. 2.18b).