Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

TRANSPORT FROM THE TRANS GOLGI NETWORK TO THE CELL EXTERIOR: EXOCYTOSIS
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delivery of membrane from the Golgi apparatus is organized so as to maintain
the differences between one cell-surface domain and another. A typical epithelial
cell, for example, has an apical domain, which faces either an internal cavity
or the outside world and often has specialized features such as cilia or a brush
border of microvilli. It also has a basolateral domain, which covers the rest of the
cell. The two domains are separated by a ring of tight junctions (see Figure 19–21),
which prevent proteins and lipids (in the outer leaflet of the lipid bilayer) from diffusing
between the two domains, so that the differences between the two domains
are maintained.
In principle, differences between plasma membrane domains need not
depend on the targeted delivery of the appropriate membrane components.
Instead, membrane components could be delivered to all regions of the cell surface
indiscriminately but then be selectively stabilized in some locations and
selectively eliminated in others. Although this strategy of random delivery followed
by selective retention or removal seems to be used in certain cases, deliveries
are often specifically directed to the appropriate membrane domain. Epithelial
cells lining the gut, for example, secrete digestive enzymes and mucus at their apical
surface and components of the basal lamina at their basolateral surface. Such
cells must have ways of directing vesicles carrying different cargoes to different
plasma membrane domains. Proteins from the ER destined for different domains
travel together until they reach the TGN, where they are separated and dispatched
in secretory or transport vesicles to the appropriate plasma membrane domain
(Figure 13–71).
The apical plasma membrane of most epithelial cells is greatly enriched in
glycosphingolipids, which help protect this exposed surface from damage—for
example, from the digestive enzymes and low pH in sites such as the gut or stomach,
respectively. Similarly, plasma membrane proteins that are linked to the lipid
bilayer by a GPI anchor (see Figure 12–52) are found predominantly in the apical
plasma membrane. If recombinant DNA techniques are used to attach a GPI
anchor to a protein that would normally be delivered to the basolateral surface,
the protein is usually delivered to the apical surface instead. GPI-anchored proteins
are thought to be directed to the apical membrane because they associate
with glycosphingolipids in lipid rafts that form in the membrane of the TGN. As
discussed in Chapter 10, lipid rafts form in the TGN and plasma membrane when
glycosphingolipids and cholesterol molecules self-associate (see Figure 10–13).
basolateral
transport
vesicle
apical
transport
vesicle
apical
plasma
membrane
basolateral
early endosome
tight junction
basolateral
plasma membrane
trans
Golgi
network
(A) DIRECT SORTING IN THE
TRANS GOLGI NETWORK
nucleus
(B) INDIRECT SORTING VIA
EARLY ENDOSOMES
Figure 13–71 Two ways of sorting
plasma membrane proteins in a
polarized epithelial cell. (A) In the direct
pathway, proteins destined for different
plasma membrane domains are sorted and
packaged into different transport vesicles.
The lipid-raft-dependent delivery system
to the apical domain described in the
text is an example of the direct pathway.
(B) In the indirect pathway, a protein is
retrieved from the inappropriate plasma
membrane domain by endocytosis and
then transported to the correct domain via
early endosomes—that is, by transcytosis.
The indirect pathway, for example, is used
in liver hepatocytes to deliver proteins to
the apical domain that lines bile ducts.