General features of receptor-mediated endocytosis

Coated pits containing receptor-bound hormones become invaginated and pinch off intracellularly to form what are called coated vesicles. The coated vesicles still have clathrin associated with them, forming basket-like structures around the ves- 

Although not as acidic as lysosomes (with an intra-compartmental pH of 4.5, see Ref. 21), the pH 5.5 environment of the endosome [22] is sufficiently low to cause the dissociation of some hormones from their receptors. When this occurs, there is a subsequent sequestering of the free hormone from the receptor in a related vesicle and tubule compartment called CURL (compartment for uncoupling of receptor from ligand, see Ref. 23), where the free hormone is sequestered into the vesicular structure while the receptor accumulates in the membrane of the tubule structure. A subsequent physical separation of these compartments allows for the differential processing of the hormone versus the receptor. Thus, while the free hormone is ultimately delivered (via vesicle fusion) to the lysosome where it is degraded, the free receptor may be recycled (via the Golgi compartment) to the cell 

It should be pointed out, however, that not all hormones dissociate from their receptor in the pH 5.5 environment of the endosome [24], Some hormone-receptor complexes require much lower pH values for dissociation to occur. Although not a peptide hormone, the iron-transport protein transferrin is a peculiar example of this phenomenon and should be pointed out. In this case, at the neutral pH of the extracellular fluid transferrin containing bound iron binds to its cell surface receptor and is internalized. In the low pH environment of the endosome, iron becomes dissociated from transferrin, but transferrin remains bound to its receptor. The transferrin receptor, with bound transferrin, is then recycled to the cell surface. With iron no longer bound to the transferrin, the transferrin readily dissociates from its receptor at the neutral pH of the extracellular fluid [25,26]. This mechanism provides for an efficient continual uptake of iron into cells. Unlike transferrin, however, in those instances where peptide hormones have been documented not to be dissociated from their receptor in the endosome compartment, the hormone and receptor are delivered to the lysosomes via fusion of the endosomes with lyso-somes, where both hormone and receptor are degraded [24,27]. The continuous degradation of the receptor with each round of RME eventually leads to a decrease in the number of receptors on the cell surface, a phenomenon called down-regulation. 

Whether a given hormone receptor is recycled or not during RME depends not only upon which hormone the receptor binds, but also upon the cell type and stage of differentiation of a given cell. Thus, the insulin receptor has been shown to be recycled during RME in rat adipocytes [28,29], but not in lymphocytes [30] and it is down-regulated in the adult rat liver [31], but not in the fetal rat liver [31]. 

Methods used to assess receptor-mediated endocytosis 

---