Macropinocytosis is another clathrin-independent endocytic mechanism that can be activated in practically all animal cells. In most cell types, it does not operate continually but rather is induced for a limited time in response to cell-surface receptor activation by specific cargoes, including growth factors, integrin ligands, apoptotic cell remnants, and some viruses. These ligands activate a complex signaling pathway, resulting in a change in actin dynamics and the formation of cell-surface protrusions, called ruffles (discussed in Chapter 16). When ruffles collapse back onto the cell, large fluid-filled endocytic vesicles form, called macropinosomes (Figure 13–50), which transiently increase the bulk fluid uptake of a cell by up to tenfold. Macropinocytosis is a dedicated degradative pathway: macropinosomes acidify and then fuse with late endosomes or endolysosomes, without recycling their cargo back to the plasma membrane.
cells use receptor-Mediated endocytosis to Import selected extracellular Macromolecules
In most animal cells, clathrin-coated pits and vesicles provide an efficient pathway for taking up specific macromolecules from the extracellular fluid. In this process, called receptor-mediated endocytosis, the macromolecules bind to
Figure 13–49 Caveolae in the plasma membrane of a fibroblast. (a) This electron micrograph shows a plasma membrane with a very high density of caveolae. (b) This rapid-freeze deep-etch image demonstrates the characteristic “cauliflower” texture of the cytosolic face of the caveolae membrane. The characteristic texture is thought to result from aggregates of caveolins and cavins. a clathrin-coated pit is also seen at the upper right. (courtesy of r.g.w. anderson, from k.g. rothberg et al., Cell 68:673–682, 1992. with permission from elsevier.) complementary transmembrane receptor proteins, which accumulate in coated pits, and then enter the cell as receptor–macromolecule complexes in clathrin-coated vesicles (see Figure 13–48). Because ligands are selectively captured by receptors, receptor-mediated endocytosis provides a selective concentrating mechanism that increases the efficiency of internalization of particular ligands more than a hundredfold. In this way, even minor components of the extracellular fluid can be efficiently taken up in large amounts. A particularly well-understood and physiologically important example is the process that mammalian cells use to import cholesterol.
Many animal cells take up cholesterol through receptor-mediated endocytosis and, in this way, acquire most of the cholesterol they require to make new membrane. If the uptake is blocked, cholesterol accumulates in the blood and can contribute to the formation in blood vessel (artery) walls of atherosclerotic plaques, deposits of lipid and fibrous tissue that can cause strokes and heart attacks by blocking arterial blood flow. In fact, it was a study of humans with a strong genetic predisposition for atherosclerosis that first revealed the mechanism of receptor-mediated endocytosis.