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

742 Chapter 13: Intracellular Membrane Traffic
newly synthesized
soluble proteins
for constitutive
secretion
Golgi apparatus
CYTOSOL
newly synthesized plasma
membrane lipids
trans
Golgi
network
secretory vesicle
storing secretory
proteins
unregulated
membrane
fusion
newly synthesized plasma
membrane protein
intracellular
signaling pathway
regulated
membrane
fusion
EXTRACELLULAR SPACE
CONSTITUTIVE
SECRETORY
PATHWAY
plasma membrane
signal such as
hormone or
neurotransmitter
REGULATED
SECRETORY
PATHWAY
Figure 13–62 The constitutive and
regulated secretory pathways. The
two pathways diverge in the TGN. The
constitutive secretory pathway operates
in all cells. Many soluble proteins are
continually secreted from the cell by
this pathway, which also supplies the
plasma membrane with newly synthesized
membrane lipids and proteins. Specialized
secretory cells also have a regulated
secretory pathway, by which selected
proteins in the TGN are diverted into
secretory vesicles, where the proteins
are concentrated and stored until an
extracellular signal stimulates their secretion.
The regulated secretion of small molecules,
such as histamine and neurotransmitters,
occurs by a similar pathway; these
molecules are actively transported from
the cytosol into preformed secretory
vesicles. There they are often bound to
specific macromolecules (proteoglycans,
for histamine) so that they can be stored at
high concentration without generating an
excessively high osmotic pressure.
delivered to different domains of the cell surface, we shall see that the options are
more complex.
Secretory Vesicles Bud from the Trans Golgi Network
Cells that are specialized for secreting some of their products rapidly on demand
concentrate and store these products in secretory vesicles (often called densecore
secretory granules because they have dense cores when viewed in the electron
microscope). Secretory vesicles MBoC6 form m13.63/13.63
from the TGN, and they release their contents
to the cell exterior by exocytosis in response to specific signals. The secreted
product can be either a small molecule (such as histamine or a neuropeptide) or
a protein (such as a hormone or digestive enzyme).
Proteins destined for secretory vesicles (called secretory proteins) are packaged
into appropriate vesicles in the TGN by a mechanism that involves the selective
aggregation of the secretory proteins. Clumps of aggregated, electron-dense
material can be detected by electron microscopy in the lumen of the TGN. The
signals that direct secretory proteins into such aggregates are not well defined
and may be quite diverse. When a gene encoding a secretory protein is artificially
expressed in a secretory cell that normally does not make the protein, the foreign
protein is appropriately packaged into secretory vesicles. This observation
ER
protein mixture
cis
Golgi
network
cis
sorting
trans
medial
Golgi
network
trans
Golgi apparatus
1 SIGNAL-MEDIATED DIVERSION
TO LYSOSOMES (VIA ENDOSOMES)
mannose 6-phosphate
receptor
CYTOSOL
2 SIGNAL-MEDIATED
DIVERSION TO SECRETORY
VESICLES (FOR REGULATED
SECRETION)
3 CONSTITUTIVE
SECRETORY
PATHWAY
plasma membrane
EXTRACELLULAR
SPACE
Figure 13–63 The three best-understood
pathways of protein sorting in the
trans Golgi network. (1) Proteins with the
mannose 6-phosphate (M6P) marker (see
Figure 13–45) are diverted to lysosomes
(via endosomes) in clathrin-coated
transport vesicles. (2) Proteins with signals
directing them to secretory vesicles are
concentrated in such vesicles as part of a
regulated secretory pathway that is present
only in specialized secretory cells. (3) In
unpolarized cells, a constitutive secretory
pathway delivers proteins with no special
features to the cell surface. In polarized
cells, such as epithelial cells, however,
secreted and plasma membrane proteins
are selectively directed to either the apical
or the basolateral plasma membrane
domain, so a specific signal must mediate
at least one of these two pathways, as we
discuss later.