Receptor - mediated endocytosis

In 1934, Lewis described the process ofpinocytosis an invagination of the plasma membrane enclosing a small droplet of fluid. Pinocytosis appeared to be a constitutive process, whereas phagocytosis described some years earlier by Metchnikoffwas regulated. Only within the last two decades has it been recognized that (i) during pinocytosis cells internalize vast amounts of membrane. indeed, more membrane than they synthesize [which led to the concept ofmembrane recycling (Steinman et al., 1983; refer to Schneider et al., 1979 a, b)] and (ii) that receptors mediate selective uptake of both macromolecules and particles. While the term endocytosis has been used to describe these processes, the term receptor-mediated endocytosis is usually reserved for specific uptake of soluble molecules. Broadly speaking, receptor-mediated endocytosis involves the movement of bound ligands from the cell surface to the interior. Whereas some ligands (e.g. ligands specific for the galactose, mannose, mannose 6-phosphate and LDL receptors) are targeted to lysosomes often subserving the nutritional needs of the cell, others (e.g. transferrin and IgG) are recycled to the plasma membrane or targeted to specific plasma membrane domains. Ligands may also be modified on entering the cell [e.g. proteolysis in macrophage endosomes (Diment & Stahl, 1984) or lysosomes, resialylation by passage through the Golgi or removal of iron in the case of transferrin (Klausner et al., 1983; Dautry-Varsat et al., 1983; Harding & Stahl, 1983)]. Intracellular transport and processing vary markedly between different receptor-ligand systems and different cell types, but these systems may be placed in four general categories (Fig. 1, Table 1). 1. Receptors that recycle but target their ligand to lysosomes. This category includes the LDL (Goldstein et al., 1979), asialoglycoprotein (Gal/GalNAc) (Schwartz et al., 1982), mannose 6-phosphate (Fischer et al., 1980 a, b), and mannose receptor systems (Stahl et al., 1980). 2. Receptors that recycle but do not target their ligand to lysosomes. The ligand remains attached to the receptor during its transit through the cell. In polarized cells this may result in transport of ligands between the apical and basolateral surfaces (transcytosis or diacytosis). Examples include transferrin and IgG (in suckling rat ileum) (Abrahamson & Rodewald, 1981). 3. Receptors that do not recycle and target their ligand to lysosomes, including the EGF receptor (Carpenter & Cohen, 1976), the insulin receptor (Kasuga et al., 1981, Carpentier et al., 1978, 1979) (insulin receptors may recycle in some cells) and the Fc receptor (in macrophages) (Mellman & Plutner, 1984) (Fc receptors may recycle under different conditions in some cells). 4. Receptors,that do not recycle and do not transport ligands to lysosomes. Transport of IgA represents a unique mechanism, transcytosis ofIgA results in cleavage and loss ofthe IgA receptor (Kuhn & Kraehenbuhl, 1979; Mostov & Blobel, 1982).