Receptor-mediated endocytosis and intracellular processing of insulin: ultrastructural and biochemical evidence for cell-specific heterogeneity and distinction from nonhormonal ligands.

This review has presented some of the data which indicate that there are substantial differences in the mechanisms of receptor-mediated uptake and intracellular processing of ligands. Data from various laboratories indicate that receptor-mediated endocytosis is not necessarily synonymous with the concentrative, coated-pit-mediated internalization of ligand-receptor complexes. That differences exist both between the internalization of different types of ligands on the same cell type and between different types of cells for same ligand has clearly been documented. The differences in mechanisms or structures involved in receptor-mediated endocytosis have been demonstrated both biochemically and ultrastructurally. The reasons for these two diverse internalization pathways utilizing coated and non-coated membrane domains are not known and require further investigation to substantiate or disprove hypotheses presented here and elsewhere. Similarly, while differences in intracellular routing of hormonal and non-hormonal ligands and their receptors certainly exist, the factors controlling the itinerary of the ligand or its receptor need to be identified. The differences in ligand-receptor processing already demonstrated should indicate that interpretation of the results of future studies must be made with a great deal of caution and conservatism particularly when attempting to apply knowledge of one ligand and cell system to pharmacologically, ultrastructurally, or physiologically dissimilar systems.