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

720 Chapter 13: Intracellular Membrane Traffic
protein folding and mediates the binding of the protein to chaperones (discussed
in Chapter 12) and lectins—for example, in guiding ER-to-Golgi transport. As we
discuss later, lectins also participate in protein sorting in the trans Golgi network.
Because chains of sugars have limited flexibility, even a small N-linked oligosaccharide
protruding from the surface of a glycoprotein (Figure 13–34) can
limit the approach of other macromolecules to the protein surface. In this way,
for example, the presence of oligosaccharides tends to make a glycoprotein more
resistant to digestion by proteolytic enzymes. It may be that the oligosaccharides
on cell-surface proteins originally provided an ancestral cell with a protective
coat; compared to the rigid bacterial cell wall, such a sugar coat has the advantage
that it leaves the cell with the freedom to change shape and move.
The sugar chains have since become modified to serve other purposes as
well. The mucus coat of lung and intestinal cells, for example, protects against
many pathogens. The recognition of sugar chains by lectins in the extracellular
space is important in many developmental processes and in cell–cell recognition:
selectins, for example, are transmembrane lectins that function in cell–cell
adhesion during blood cell migration, as discussed in Chapter 19. The presence
of oligosaccharides may modify a protein’s antigenic and functional properties,
making glycosylation an important factor in the production of proteins for
pharmaceutical purposes.
Glycosylation can also have important regulatory roles. Signaling through
the cell-surface signaling receptor Notch, for example, is an important factor in
determining the cell’s fate in development (discussed in Chapter 21). Notch is a
transmembrane protein that is O-glycosylated by addition of a single fucose to
some serines, threonines, and hydroxylysines. Some cell types express an additional
glycosyl transferase that adds an N-acetylglucosamine to each of these
fucoses in the Golgi apparatus. This addition changes the specificity of Notch for
the cell-surface signal proteins that activate it.
Man
(A)
Man
Man
GlcNAc
GlcNAc
asparagine
GlcNAc
(B)
Figure 13–34 The three-dimensional
structure of a small N-linked
oligosaccharide. The structure was
determined by x-ray crystallographic
analysis of a glycoprotein. This
oligosaccharide contains only 6 sugars,
whereas there are 14 sugars in the N-linked
oligosaccharide that is initially transferred to
proteins in the ER (see Figure 12–47).
(A) A backbone model showing all atoms
except hydrogens; only the asparagine
of the protein is shown. (B) A space-filling
model, with the asparagine and sugars
indicated using the same color scheme as
in (A). (B, courtesy of Richard Feldmann.)
MBoC6 m13.34/13.34
Transport Through the Golgi Apparatus May Occur by Cisternal
Maturation
It is still uncertain how the Golgi apparatus achieves and maintains its polarized
structure and how molecules move from one cisterna to another, and it is likely
that more than one mechanism is involved in each case. One hypothesis, called
the cisternal maturation model, views the Golgi cisternae as dynamic structures
that mature from early to late by acquiring and then losing specific Golgi-resident
proteins. According to this view, new cis cisternae continually form as vesicular
tubular clusters arrive from the ER and progressively mature to become a medial
cisterna and then a trans cisterna (Figure 13–35A). A cisterna therefore moves
through the Golgi stack with cargo in its lumen. Retrograde transport of the Golgi
enzymes by budding COPI-coated vesicles explains their characteristic distribution.
As we discuss later, when a cisterna finally moves forward to become part of
the trans Golgi network, various types of coated vesicles bud off it until this network
disappears, to be replaced by a maturing cisterna just behind. At the same
time, other transport vesicles are continually retrieving membrane from post-
Golgi compartments and returning it to the trans Golgi network.
The cisternal maturation model is supported by studies using Golgi enzymes
from different cisternae that were fluorescently labeled with different colors. Such
studies performed in yeast cells where Golgi cisternae are not stacked reveal that
individual Golgi cisternae change their color, thereby demonstrating that they
change their complement of resident enzymes as they mature, even though they
are not stacked. In further support of the model, electron microscopic observations
found that large structures such as procollagen rods in fibroblasts and scales
in certain algae move progressively through the Golgi stack.
An alternative view holds that Golgi cisternae are long-lived structures that
retain their characteristic set of Golgi-resident proteins firmly in place, and cargo
proteins are transported from one cisterna to the next by transport vesicles (Figure
13–35B). According to this vesicle transport model, retrograde flow of vesicles