Ganong's Review of Medical Physiology, 23rd Edition

44 SECTION I Cellular & Molecular Basis of Medical Physiology
Exocytosis
Endocytosis
FIGURE 2–12 Exocytosis and endocytosis. Note that in exocytosis the cytoplasmic sides of two membranes fuse, whereas in endocytosis
two noncytoplasmic sides fuse. (Reproduced with permission from Alberts B et al: Molecular Biology of the Cell, 4th ed. Garland Science, 2002.)
the clathrin molecules form a geometric array that surrounds
the endocytotic vesicle. At the neck of the vesicle, the GTP
binding protein dynamin is involved, either directly or indirectly,
in pinching off the vesicle. Once the complete vesicle is
formed, the clathrin falls off and the three-legged proteins recycle
to form another vesicle. The vesicle fuses with and dumps its
contents into an early endosome (Figure 2–11). From the early
endosome, a new vesicle can bud off and return to the cell
membrane. Alternatively, the early endosome can become a
late endosome and fuse with a lysosome (Figure 2–11) in
which the contents are digested by the lysosomal proteases.
Clathrin-mediated endocytosis is responsible for the internal-
FIGURE 2–13 Clathrin molecule on the surface of an
endocytotic vesicle. Note the characteristic triskelion shape and the
fact that with other clathrin molecules it forms a net supporting the
vesicle.
Cytoplasm
ization of many receptors and the ligands bound to them—
including, for example, nerve growth factor and low-density
lipoproteins. It also plays a major role in synaptic function.
It is apparent that exocytosis adds to the total amount of
membrane surrounding the cell, and if membrane were not
removed elsewhere at an equivalent rate, the cell would
enlarge. However, removal of cell membrane occurs by
endocytosis, and such exocytosis–endocytosis coupling maintains
the surface area of the cell at its normal size.
RAFTS & CAVEOLAE
Some areas of the cell membrane are especially rich in cholesterol
and sphingolipids and have been called rafts. These rafts
are probably the precursors of flask-shaped membrane depressions
called caveolae (little caves) when their walls become
infiltrated with a protein called caveolin that resembles
clathrin. There is considerable debate about the functions of
rafts and caveolae, with evidence that they are involved in cholesterol
regulation and transcytosis. It is clear, however, that
cholesterol can interact directly with caveolin, effectively limiting
the protein’s ability to move around in the membrane.
Internalization via caveolae involves binding of cargo to caveolin
and regulation by dynamin. Caveolae are prominent in
endothelial cells, where they help in the uptake of nutrients
from the blood.