362
Cell Junctions, Structure, Function, and Regulation
adjacent cells come into such close prox-
imity that the outer leaflets of the adjacent
plasma membranes appear to be fused.
The anastomosing Flaments of tTJs are
best observed using freeze fracture as
s
h
ow
ni
i
g
.1
3
(
a
)
r
e
e
z
ef
r
a
c
t
u
r
ei
s
a platinum carbon replica of a fractured
membrane surface that provides a three-
dimensional relief of the junction when
viewed by scanning electron microscopy.
This technique creates an image of either
strands of beads on the protoplasmic face
or grooves on the exoplasmic face.
Early hypotheses speculated that the
tight junction may be formed by special-
ized lipid arrangements between the two
plasma membranes of adjacent cells; how-
ever, more recent studies have shown that
transmembrane proteins are responsible
for the ultrastructure of the tight junc-
tion (±ig. 13c). In a manner similar to
AJs and desmosomes, the transmembrane
proteins of TJs attach to the cytoskele-
ton through linker proteins and contain
scaffolding proteins that allow TJs to
participate in a number of signal trans-
duction pathways.
2.5.1
Claudins and Other TJ
Transmembrane Proteins
Initial studies using transepithelial electri-
cal resistance (TER) to assess the barrier
function of an epithelial monolayer sug-
gested a relationship between the num-
ber of tight junction strands and TER.
However, this concept was challenged by
studies using Madin-Darby canine kid-
ney (MDCK) epithelial cells, a cell line
that is used extensively for
in vitro
stud-
ies of the epithelial barrier as they form
functionally intact TJs. Interestingly, two
strains of MDCK cells had been identiFed
that had vastly different TERs (MDCK I
3000
Ä
cm
2
and MDCK II
100
Ä
cm
2
),
but possessed the same number of tight
junction strands with the same morphol-
ogy. This suggested that in addition to
the number of tight junction strands, the
Cytoplasmic
surface
Tight-junction
strand
Kissing
point
Extracellular
space
(a)
(b)
(c)
Mv
Ap
Bl
Fig. 13
Ultrastructure of tight junctions.
(a) Electron microscopic image showing
freeze-fracture replica of the tight junctions in
intestinal epithelial cells. The interconnected
strands appear as Fbers on the P-face (arrow
heads) and as grooves on the E-face (arrows).
(b) Electron micrograph showing the close
association of the plasma membranes in tight
junction strands. Note the dense plaque region
associated with the junction. (c) Schematic
showing the ‘‘kissing point’’ produced by protein
interactions on adjacent cells; this interaction
produces the close association of membranes
shown by arrow heads in (b).
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