Ligand Binding and Processing: The Perfused Liver as a Model System

Receptor-mediated endocytosis is the process used by all eukaryotic cells to internalize a variety of biologically important macromolecules, e.g., transport proteins that deliver nutrients to cells (1 ,2 ), plasma proteins (3 ), hormones and growth factors (4 ,5 ), and lysosomal enzymes (6 ). The process is initiated when cell surface proteins (receptors) bind specific macromolecules (ligands) with high affinity at the plasma membrane. Following ligand binding, receptor-ligand complexes are rapidly internalized through clathrin-coated pits and delivered to endosomes. In endosomes, sorting and segregation of ligands and receptors into one of several pathways occur (7 ). For example, some receptors recycle to the cell surface while their ligands are degraded to amino acids in lysosomes, whereas in other cases, both are degraded or recycled. In hepatocytes, receptors and ligand may also be transported across the cell via a process called transcytosis.