The endocytic part of the cycle often begins at clathrin-coated pits. These specialized regions typically occupy about 2% of the total plasma membrane area. The lifetime of a clathrin-coated pit is short: within a minute or so of being formed, it invaginates into the cell and pinches off to form a clathrin-coated vesicle (Figure 13–48). About 2500 clathrin-coated vesicles pinch off from the plasma membrane of a cultured fibroblast every minute. The coated vesicles are even more transient than the coated pits: within seconds of being formed, they shed their coat and fuse with early endosomes.
not all pinocytic vesicles are clathrin-coated
In addition to clathrin-coated pits and vesicles, cells can form other types of pinocytic vesicles, such as caveolae (from the Latin for “little cavities”), originally recognized by their ability to transport molecules across endothelial cells that form the inner lining of blood vessels. Caveolae, sometimes seen in the electron microscope as deeply invaginated flasks, are present in the plasma membrane of most vertebrate cell types (Figure 13–49). They are thought to form from lipid rafts in the plasma membrane (discussed in Chapter 10), which are especially rich
Figure 13–48 The formation of clathrincoated vesicles from the plasma membrane. These electron micrographs illustrate the probable sequence of events in the formation of a clathrin-coated vesicle from a clathrin-coated pit. The clathrincoated pits and vesicles shown are larger than those seen in normal-sized cells; they are from a very large hen oocyte and they take up lipoprotein particles to form yolk. The lipoprotein particles bound to their membrane-bound receptors appear as a dense, fuzzy layer on the extracellular surface of the plasma membrane—which is the inside surface of the coated pit and vesicle. (courtesy of M.M. perry and a.b. gilbert, J. Cell sci. 39:257–272, 1979. with permission from The company of biologists.) 0.2 µm in cholesterol, glycosphingolipids, and glycosylphosphatidylinositol (GPI)-anchored membrane proteins (see Figure 10–13). The major structural proteins in caveolae are caveolins, a family of unusual integral membrane proteins that each insert a hydrophobic loop into the membrane from the cytosolic side but do not extend across the membrane. On their cytosolic side, caveolins are bound to large protein complexes of caving proteins, which are thought to stabilize the membrane curvature.
In contrast to clathrin-coated and COPIor COPII-coated vesicles, caveolae are usually static structures. Nonetheless, they can be induced to pinch off and serve as endocytic vesicles to transport cargo to early endosomes or to the plasma membrane on the opposite side of a polarized cell (in a process called transcytosis, which we discuss later). Some animal viruses such as SV40 and papillomavirus (which causes warts) enter cells in vesicles derived from caveolae. The viruses are first delivered to early endosomes and move from there in transport vesicles to the lumen of the ER. The viral genome exits across the ER membrane into the cytosol, from where it is imported into the nucleus to start the infection cycle. Cholera toxin (discussed in Chapters 15 and 19) also enters the cell through caveolae and is transported to the ER before entering the cytosol.