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

1050 Chapter 19: Cell Junctions and the Extracellular Matrix
intercellular
space
sealing
strands of
occludin and
claudin
proteins
interacting
plasma membranes
cell 1
C
cell 2
(B)
N
C
N
claudin occludin
tight-junction proteins
Figure 19–21 A model of a tight junction.
(A) The sealing strands hold adjacent
plasma membranes together. The strands
are composed of transmembrane proteins
that make contact across the intercellular
space and create a seal. (B) The molecular
composition of a sealing strand. The
major extracellular components of the
tight junction are members of a family of
proteins with four transmembrane domains.
One of these proteins, claudin, is the most
important for the assembly and structure
of the sealing strands, whereas the related
protein occludin has the less critical role of
determining junction permeability. The two
termini of these proteins are both on the
cytoplasmic side of the membrane, where
they interact with large scaffolding proteins
that organize the sealing strands and link
the tight junction to the actin cytoskeleton
(not shown here, but see Figure 19–22).
(A)
cell
1
cell
2
0.3 µm
consist of strings of protein-binding domains, typically including several PDZ
domains—segments about 80 amino acids long that can recognize and bind the
C-terminal tails of specific partner proteins (Figure 19–22). One domain of these
scaffold proteins can attach to MBoC6 a claudin m19.26/19.21
protein, while others can attach to occludin
or the actin cytoskeleton. Moreover, one molecule of scaffold protein can bind
to another. In this way, the cell can assemble a mat of intracellular proteins that
organizes and positions the sealing strands of the tight junction.
The tight-junctional network of sealing strands usually lies just apical to adherens
and desmosome junctions that bond the cells together mechanically; the
whole assembly is called a junctional complex (see Figure 19–2). The parts of this
junctional complex depend on each other for their formation. For example, anticadherin
antibodies that block the formation of adherens junctions also block the
formation of tight junctions.
Gap Junctions Couple Cells Both Electrically and Metabolically
Tight junctions block the passageways through the gaps between epithelial cells,
preventing extracellular molecules from leaking from one side of an epithelium to
the other. Another type of junctional structure has a radically different function:
it bridges gaps between adjacent cells so as to create direct channels from the
ZO-1
domains
ZO-2
domains
ZO-3
domains
N
N
N
claudin
ZO
proteins
signaling
proteins
occludin
PDZ PDZ PDZ SH3 GK P
PDZ PDZ PDZ SH3 GK P
actin
PDZ PDZ P PDZ SH3 GK
Figure 19–22 Scaffold proteins at the
tight junction. The scaffold proteins ZO-1,
ZO-2, and ZO-3 are concentrated beneath
the plasma membrane at tight junctions.
Each of the proteins contains multiple
protein-binding domains, including three
PDZ domains, an SH3 domain, and a GK
domain, linked together like beads on a
flexible string. These domains enable the
proteins to interact with each other and
with numerous other partners, as indicated
here, to generate a tightly woven protein
network that organizes the sealing strands
of the tight junction and links them to
the actin cytoskeleton. Scaffold proteins
with similar structure help organize other
junctional complexes, including those at
neural synapses.