Topic 4.4 - Post-Golgi Traffic
In this topic we examine the 2 major pathways that newly synthesized proteins will take: The secretory
pathway (aka exocytosis) and the Lysosomal Pathway.
As discussed in the previous topic, each Golgi stack has two faces, the cis face and the transface. The flow of
material in the Golgi apparatus is from cis to trans. Transport vesicles from the ER containing membrane and
soluble proteins fuse with the cis face of the Golgi. Proteins then move from the cis cisternae, to the medial,
then to the trans citsernae. As the proteins move along they are sorted, based on a combination of the chemical
features of the protein itself, and there is an increase in the acidity inside the Golgi as the protein moves
from cis to trans. From the trans Golgi Network (TGN), there are 2 main destinations, via 3 distinct pathways:
Proteins get incorporated into dense core secretory vesicles that are then released to the extracellular
space via the Regulated Secretory Pathway in response to a specific stimulus.
These proteins are capable of forming aggregates in acidic conditions of the transGolgi network
(TGN). The earlier stages of the secretory pathway in which aggregation does not occur are at
neutral pH (How might the properties of the proteins help with this?)
Vesicles containing membrane and proteins that are released continuously to the cell surface via
the Constitutive Secretory Pathway.
The proteins destined for the constitutive secretory pathway do not form aggregates in
the trans Golgi network.
Finally, proteins can be destined for the lysosomes via the Lysosomal Pathway. We will talk of this in
more detail below.
Proteins destined for the lysosomal pathway are glycosylated, which adds a special targeting
The Secretory Pathway (aka Exocytosis)
Overview: There are two different secretory pathways through which
proteins can exit the cell: the Regulated Pathway and the Constitutive
In the Regulated Pathway proteins are consolidated into vesicles
that are stored in the cell until they are secreted in response to a
In the Constitutive Pathway vesicles continuously form and carry
proteins from the Golgi to the cell surface.
As we've seen over and over, the proteins carry within their chemical
structure the information needed to determine which pathway they
belong in. The primary site for sorting of proteins into one of these
pathways is the trans-most cisternae, also known as the trans Golgi
Network. The trans Golgi Network is Where Protein Sorting Takes Place
2 different types of exocytosis, based on the properties of the proteins that are being sorted.
Protein Sorting: Constitutive versus Regulated Secretion
How are proteins targeted to the different secretory pathways? The fates of the proteins are thought to be
determined by features carried by the proteins themselves (How might this work? Think back to Unit 2).
Proteins destined for the regulated secretory pathway form aggregates in the TGN,
while those destined for the constitutive secretory pathway do not.
Aggregates (i.e. a bunch of proteins that have clumped together) containing proteins destined for regulated
secretion can be captured by TEM in vesicles in the process of budding from the trans Golgi network. The
aggregation occurs in response to the acidic conditions of the transGolgi network. Experimental evidence
shows that proteins that are normally secreted via the regulated secretory pathway also form aggregates in
vitro (what does this mean?) when incubated under the ionic and pH conditions that occur in the trans Golgi
network (pH 6.5, 1 mM Ca ). Aggregation does not occur under the more pH neutral conditions of the earlier
parts of the secretory pathway. These protein aggregates give rise to the 'dense core secretory granules' that are
considered to be the typical storage vesicles of the regulated secretory pathway (shown below).
Insulin containing dense core
secretory in a islet beta cell of
the pancreas. One of the
granules in being exocytosed. The regulated secretory pathway is used for proteins that are stored and secreted on demand. For example,
insulin is produced by the beta cells of the pancreas and stored in dense core secretory granules. When blood
sugar increases to a threshold level, insulin containing secretory granules fuse with the plasma membrane,
releasing insulin to the blood, as shown above. The digestive enzymes produced by the acinar cells of the
pancreas are stored in dense core granules called zymogen granules and are released into the duct leading to the
gut following feeding.
As noted when we discussed protein import, proteolytic cleavage of many secreted proteins occurs during the
maturation of dense core secretory granules.
The regulated exocytosis pathway operates in cells specialized for secretion and produces cell product on
demand. These proteins form aggregates in the trans Golgi network and are packaged into dense core granules.
These granules are stored in the cytoplasm until the cell is ready to secrete them. Examples include digestive
enzymes in the acinar cells of the pancreas, insulin from the beta cells