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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cis Golgi network
Golgi stack
immature secretory vesicle
clathrin-coated
retrieval vesicle
Golgi
cisterna
trans Golgi
network
clathrin
immature
secretory vesicle
mature
secretory
vesicle
(A)
CARGO CONCENTRATION
(B)
trans Golgi network
200 nm
mature secretory
vesicle
shows that, although the proteins that an individual cell expresses and packages
in secretory vesicles differ, they contain common sorting signals, which function
properly even when the proteins are expressed in cells that do not normally make
them.
It is unclear how the aggregates of secretory proteins are segregated into secretory
vesicles. Secretory vesicles have unique proteins in their membrane, some of
which might serve as receptors for aggregated protein MBoC6 in m13.65/13.65
the TGN. The aggregates
are much too big, however, for each molecule of the secreted protein to be bound
by its own cargo receptor, as occurs for transport of the lysosomal enzymes. The
uptake of the aggregates into secretory vesicles may therefore more closely resemble
the uptake of particles by phagocytosis at the cell surface, where the plasma
membrane zippers up around large structures.
Initially, most of the membrane of the secretory vesicles that leave the TGN is
only loosely wrapped around the clusters of aggregated secretory proteins. Morphologically,
these immature secretory vesicles resemble dilated trans Golgi cisternae
that have pinched off from the Golgi stack. As the vesicles mature, they
fuse with one another and their contents become concentrated (Figure 13–64A),
probably as the result of both the continuous retrieval of membrane that is recycled
to the TGN, and the progressive acidification of the vesicle lumen that results
from the increasing concentration of V-type ATPases in the vesicle membrane
that acidify all endocytic and exocytic organelles (see Figure 13–37). The degree of
concentration of proteins during the formation and maturation of secretory vesicles
is only a small part of the total 200–400-fold concentration of these proteins
that occurs after they leave the ER. Secretory and membrane proteins become
concentrated as they move from the ER through the Golgi apparatus because of
an extensive retrograde retrieval process mediated by COPI-coated transport vesicles
that carry soluble ER resident proteins back to the ER, while excluding the
secretory and membrane proteins (see Figure 13–25).
Membrane recycling is important for returning Golgi components to the Golgi
apparatus, as well as for concentrating the contents of secretory vesicles. The vesicles
that mediate this retrieval originate as clathrin-coated buds on the surface of
immature secretory vesicles, often being seen even on budding secretory vesicles
that have not yet pinched off from the Golgi stack (Figure 13–64B).
Because the final mature secretory vesicles are so densely filled with contents,
the secretory cell can disgorge large amounts of material promptly by exocytosis
when triggered to do so (Figure 13–65).
Figure 13–64 The formation of
secretory vesicles. (A) Secretory
proteins become segregated and highly
concentrated in secretory vesicles by two
mechanisms. First, they aggregate in the
ionic environment of the TGN; often the
aggregates become more condensed as
secretory vesicles mature and their lumen
becomes more acidic. Second, clathrincoated
vesicles retrieve excess membrane
and lumenal content present in immature
secretory vesicles as the secretory vesicles
mature. (B) This electron micrograph shows
secretory vesicles forming from the TGN in
an insulin-secreting β cell of the pancreas.
Anti-clathrin antibodies conjugated to gold
spheres (black dots) have been used to
locate clathrin molecules. The immature
secretory vesicles, which contain insulin
precursor protein (proinsulin), contain
clathrin patches, which are no longer
seen on the mature secretory vesicle. (B,
courtesy of Lelio Orci.)
Precursors of Secretory Proteins Are Proteolytically Processed
During the Formation of Secretory Vesicles
Concentration is not the only process to which secretory proteins are subjected as
the secretory vesicles mature. Many protein hormones and small neuropeptides,