ﬂ uid). A similar process allows small amounts of macromol-
ecules to move across the intestinal epithelium.
Most endocytotic vesicles fuse with a series of intra-
cellular vesicles and tubular elements known as endosomes
(Chapter 3), which lie between the plasma membrane and the
Golgi apparatus. Like the Golgi apparatus, the endosomes
perform a sorting function, distributing the contents of the
vesicle and its membrane to various locations. Some of the
contents of endocytotic vesicles are passed from the endo-
somes to the Golgi apparatus, where the ligands are modiﬁ ed
and processed. Other vesicles fuse with lysosomes, organelles
that contain digestive enzymes that break down large mole-
cules such as proteins, polysaccharides, and nucleic acids. The
fusion of endosomal vesicles with the lysosomal membrane
exposes the contents of the vesicle to these digestive enzymes.
Finally, in many cases, the receptors that were internalized
with the vesicle get recycled back to the plasma membrane.
Another fate of endocytotic vesicles is seen in a special
type of receptor-mediated endocytosis called potocytosis.
is similar to other types of receptor-mediated
endocytosis in that an extracellular ligand typically binds to a
plasma membrane receptor, initiating formation of an intracel-
lular vesicle. In potocytosis, however, the ligands appear to be
primarily restricted to low-molecular-weight molecules such
as certain vitamins, but have also been found to include the
lipoprotein complexes just described. Potocytosis differs from
clathrin-dependent, receptor-mediated endocytosis in the fate
of the endocytotic vesicle. In potocytosis, tiny vesicles called
(singular: caveolus, “little caves”) pinch off from the
plasma membrane and deliver their contents directly to the cell
cytosol, rather than merging with lysosomes or other organ-
elles. The small molecules within the caveolae may diffuse
into the cytosol via channels, or be transported by carriers.
Although their functions are still being actively investigated,
caveolae have been implicated in a variety of important cellu-
lar functions, including cell signaling, transcellular transport,
and cholesterol homeostasis.
Each episode of endocytosis removes a small portion
of the membrane from the cell surface. In cells that have a
great deal of endocytotic activity, more than 100 percent of
the plasma membrane may be internalized in an hour, yet the
membrane surface area remains constant. This is because the
membrane is replaced at about the same rate by vesicle mem-
brane that fuses with the plasma membrane during
Some of the plasma membrane proteins taken into the cell dur-
ing endocytosis are stored in the membranes of endosomes,
and upon receiving the appropriate signal can be returned to
fuse with the plasma membrane during exocytosis.
Exocytosis performs two functions for cells: (1) It provides a
way to replace portions of the plasma membrane that endocy-
tosis has removed, and, in the process, to add new membrane
components as well, and (2) it provides a route by which mem-
brane-impermeable molecules (such as protein hormones) the
cell synthesizes can be secreted into the extracellular ﬂ
How does the cell package substances that are to be
secreted by exocytosis into vesicles? Chapter 3 described the
entry of newly formed proteins into the lumen of the endo-
plasmic reticulum and the protein’s processing through the
Golgi apparatus. From the Golgi apparatus, the proteins to be
secreted travel to the plasma membrane in vesicles from which
they can be released into the extracellular ﬂ uid by exocytosis.
Very high concentrations of various organic molecules, such
as neurotransmitters, can be held within vesicles by employing
a combination of mediated transport across the vesicle mem-
brane and binding of the transported substances to proteins
within the vesicle.
The secretion of substances by exocytosis is triggered in
most cells by stimuli that lead to an increase in cytosolic cal-
cium concentration in the cell. As will be described in Chapters
5 and 6, these stimuli open calcium channels in the plasma
membrane and/or the membranes of intracellular organelles.
The resulting increase in cytosolic calcium concentration acti-
vates proteins required for the vesicle membrane to fuse with
the plasma membrane and release the vesicle contents into
the extracellular ﬂ
uid. Material stored in secretory vesicles is
available for rapid secretion in response to a stimulus, without
delays that might occur if the material had to be synthesized
after the stimulus arrived.
Epithelial cells line hollow organs or tubes and regulate the
absorption or secretion of substances across these surfaces.
One surface of an epithelial cell generally faces a hollow or
ﬂ uid-ﬁ lled chamber, and the plasma membrane on this side
is referred to as the
(also known as the
apical, or mucosal, membrane) of the epithelium. The plasma
membrane on the opposite surface, which is usually adjacent
to a network of blood vessels, is referred to as the
(also known as the serosal membrane).
There are two pathways by which a substance can cross
a layer of epithelial cells: (1) by diffusion
cells of the epithelium—the
or (2) by
an epithelial cell across either the luminal or
basolateral membrane, diffusion through the cytosol, and exit
across the opposite membrane. This is termed the
Diffusion through the paracellular pathway is limited by
the presence of tight junctions between adjacent cells, because
these junctions form a seal around the luminal end of the epithe-
lial cells (Chapter 3). Although small ions and water can diffuse
to some degree through tight junctions, the amount of paracel-
lular diffusion is limited by the tightness of the junctional seal
and the relatively small area available for diffusion. The leakiness
of the paracellular pathway varies in different types of epithe-
lium, with some being very leaky and others very tight.
During transcellular transport, the movement of mole-
cules through the plasma membranes of epithelial cells occurs
via the pathways (diffusion and mediated transport) already
described for movement across membranes. However, the
transport and permeability characteristics of the luminal and
basolateral membranes are not the same. These two mem-
branes contain different ion channels and different transport-
ers for mediated transport. As a result of these differences,