Endocytosis receptor-mediated ligand degradation

In contrast, receptor-mediated endocytosis is very specific. Embedded in the membrane are proteins with specific receptor sites exposed to the extracellular fluid. The receptor proteins are usually clustered in regions of the membrane called coated pits, which are lined on their cytoplasmic side by a fuzzy layer consisting of a protein called clathrin. When ligands bind to the receptor sites, they are carried into the cell by the inward budding of a coated pit to form a coated vesicle. Clathrin-coated vesicles become uncoated and fuse to form an endosome. Ligand and receptor dissociate within the endosome, and the receptor shuttles back to the cell surface. The endosome fuses with the lysosome on which ligand degradation occurs. 

While the events in receptor-mediated lipoprotein uptake are best characterized for the LDL receptor, they probably are representative of common mechanisms for the receptor-mediated endocytosis of other lipoproteins as well as for many other nonlipoprotein ligands. Individual lipoprotein receptor systems appear to differ primarily with respect to the lipoproteins recognized and the regulatory events which follow internalization and degradation. 

Most mammalian cells produce cell-surface receptors that specifically bind to apoB-100 and internalize LDL particles by receptor-mediated endocytosis. After endocytosis, the LDL particles are transported to lysosomes via the en-docytlc pathway and then are degraded by lysosomal hydrolases. LDL receptors, which dissociate from their ligands in the late endosome, recycle to the cell surface. 

Figure 5.18 Receptor-mediated endocytosis. (a) Schematic diagram of the main steps in the endocytotic pathway. Binding at the cell surface induces clustering of receptor-ligand complexes in specialized regions of the membrane. Endocytotic vesicles form in these regions separation of receptor and ligand occurs as the endosome matures. Separated receptors can recycle to the surface, while remaining material is degraded within lysosomes. (b) Typical time course of internalization and degradation.

During receptor-mediated endocytosis (for rev. see Goldstein et al. 1979) the ligand remains associated with the transport vehicle within the cell the complex dissociates and the ligand is finally degraded (Bridges et al. 1982). The constant of internalization is 3.1 x 10 - sec., while the dissociation constant has a value of... 

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