EXPERIMENTAL FIGURE 14-26 The initial stages of receptor-mediated endocytosis of low-density lipoprotein (LDL) particles are revealed by electron microscopy. Cultured human fibroblasts were incubated in a medium containing LDL particles covalently linked to the electron-dense, iron-containing protein ferritin; each small iron particle in ferritin is visible as a small dot under the electron microscope. Cells were initially incubated at 4 °C; at this temperature LDL can bind to its receptor, but internalization does not occur. After excess LDL not bound to the cells was washed away, the cells were warmed to 37 °C and then prepared for microscopy at periodic intervals. (a) A coated pit, showing the clathrin coat on the inner (cytosolic) surface of the pit, soon after the temperature was raised. (b) A pit containing LDL apparently closing on itself to form a coated vesicle. (c) A coated vesicle containing ferritin-tagged LDL particles. (d) Ferritin-tagged LDL particles in a smooth-surfaced early endosome 6 minutes after internalization began. See also M. S. Brown and J. Goldstein, 1986, Science 232:34.

[Photographs republished with permission of Nature, from Goldstein, J. et al., “Coated pits, coated vesicles, and receptor-mediated endocytosis,” 1979, Nature 279:679–685; permission conveyed through the Copyright Clearance Center, Inc.]