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FIGURE 14.22 Receptor mediated endocytosis [49] .
RME begins with a ligand binding to a specific receptor that spans the plasma membrane
( Figure 14.22 , [49] ). Examples of these ligands include hormones, growth factors, enzymes,
serum proteins, LDL (with attached cholesterol), transferrin (with attached iron), antibodies,
some viruses, and even bacterial toxins. After receptor binding, the complex diffuses laterally
in the plasma membrane until it encounters a specialized patch of membrane called a coated
pit. The receptor-ligand complexes accumulate in these patches as do other proteins
including clathrin, adaptor protein, and dynamin. Since coated pits occupy ~20% of the
plasma membrane surface area, they are not minor membrane features. The collection of
these proteins starts to curve a section of the membrane that eventually pinches off to
form an internalized coated vesicle. Clathrin and dynamin then recycle back to the plasma
membrane leaving an uncoated vesicle that is free to fuse with an early endosome. After
the early endosomes mature into late endosomes, they then go on to the lysosome for diges-
tion. RME is a very fast process. Invagination and vesicle formation takes ~1 min. One single
cultured fibloblast cell can produce 2,500 coated pits per minute.
One example of RME has received a great deal of attention because of its essential role in
human health, namely maintaining the proper level of cholesterol in the body. Malfunctions
in the RME process for uptake of the cholesterol carrying LDL lead to hypercholesterolemia
and cardiovascular disease [46,50] . RME and its role in cholesterol metabolism was discov-
ered by Michael Brown and Joseph Goldstein ( Figure 14.23 ) of the University of Texas Health
Science Center in Dallas (now the UT Southwestern Medical Center) who received the 1985
Nobel Prize in Physiology and Medicine for their iconic work.
Pinocytosis and Phagocytosis
Two similar transport processes that have been known for a long time are pinocytosis and
phagocytosis [51] . Both involve non-specific uptake (endocytosis) of many things fromwater
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