Endocytosis: Receptor‐Mediated

Abstract

Specific receptors on the surface of mammalian cells actively internalize cell‐impermeable ligands by the mechanism of receptor‐mediated endocytosis (RME). This process is critical for the acquisition of nutrients, signal transduction, development, neurotransmission, and cellular homeostasis. Binding of ligands to internalizing receptors on the plasma membrane results in clustering of the complex in clathrin‐coated pits or other dynamic membrane regions. Invagination of these regions yields intracellular vesicles that fuse to form membrane‐sealed endosomes. Receptors typically dissociate from ligands in these acidic compartments, which allows the free receptor to cycle back to the cell surface, whereas ligands are often degraded on delivery to lysosomes, which liberates amino acids and other nutrients. By mimicking endogenous ligands, certain protein toxins, viruses, and other pathogens exploit RME to enter the cytoplasm or reach other intracellular destinations. Similarly, artificial delivery systems that mimic ligands or receptors can enhance efficiently the cellular uptake of impermeable molecules, including drugs, proteins, and nucleic acids. Advances in small‐molecule probes, structural biology, and genetic methods are beginning to illuminate the complex mechanisms of this process at the molecular level.