Frederick R. Maxfield

Mammalian cells take up extracellular material by a variety of different mechanisms that are collectively termed endocytosis. Endocytic mechanisms serve many important cellular functions including the uptake of extracellular nutrients, regulation of cell-surface receptor expression, maintenance of cell polarity, and antigen presentation. Endocytic pathways are also utilized by viruses, toxins, and symbiotic microorganisms to gain entry into cells. One of the best-characterized endocytic mechanisms is receptor-mediated endocytosis via clathrin-coated pits. This type of endocytosis constitutes the major emphasis of this review, with a brief discussion of other endocytic mechanisms and their comparison with the receptor-mediated pathway. This review describes and evaluates critically current understanding of the mechanisms of entry of plasma membrane components such as the receptor-ligand complexes and membrane lipids as well as the extracellular fluid into cells. The intracellular sorting and trafficking of these molecules upon internalization are also described. The roles of endocytosis in physiological and pathological processes are discussed. These include maintenance of cell polarization, antigen presentation, glucose transport, atherosclerosis, Alzheimer's disease, and the endocytosis of toxins and viruses.

The binding and internalization of 125I-epidermal growth factor (125I-EGF) was studied in cultures of BALB 3T3 cells using a novel method that involved removal of cell-surface hormone by treatment with acetic acid under conditions that did not remove internalized hormone. In control cultures, 125I-EGF initially bound to its receptor on the plasma membrane and then was rapidly internalized. After 30 min, only 15% of the cell-bound hormone remained on the surface. In contrast, cultures treated with dansylcadaverine retained 82% of the cell-bound hormone on the cell surface. We propose that dansylcadaverine inhibits EGF internalization by preventing it from clustering in clathrin-coated pits.