Cell Junctions, Structure, Function, and Regulation
exhibit lethality at embryonic day 9.5 due
impaired remodeling and maturation of
blood vessels.
In vitro
studies also support
the roles of plakoglobin and DP in attach-
ing VE-cadherin to intermediate Flaments,
as expression of these three components
of the complexus AJ will induce the forma-
tion of cell–cell junctions in Fbroblasts.
One should note that, to date, VE-cadherin
is the only cadherin from the type I and
type II families to form attachments to
intermediate Flaments and the actin cy-
toskeleton. Thus, VE-cadherin is a very
unique member of the cadherin super-
Functions of Desmosomes
The previous discussion highlights the
importance of desmosomes in the mainte-
nance of tissue integrity. However, recent
studies suggest that desmosomes may
mediate other functions in addition to
providing strong cell–cell adhesion. ±or
example, desmosomal adhesion has been
implicated in morphogenic cell position-
ing in the mammary gland.
In vivo
luminal epithelial cells of the mammary
gland possess desmosomal adhesions me-
diated by Dsg2/Dsc2, while the myoep-
ithelial cells surrounding the luminal cells
have desmosomes containing Dsg3/Dsc3
in addition to Dsg2/Dsc2. Isolating these
cells from tissue and allowing them to
recombine in culture results in the forma-
tion of aggregates in which the Dsg3/Dsc3
myoepithelial cells surround the lumi-
peptides homologous to Dsg3/Dsc3 in-
hibited the correct association of these
cells, suggesting that Dsg3/Dsc3-mediated
adhesion is required for the sorting of
mammary epithelial cells into appropriate
cell layers.
In addition to regulating morphogene-
sis, desmosomes may also play a role in
regulating differentiation. Recent studies
demonstrated that the ratio of Dsg1 to
Dsg3 expression varies in different epithe-
lial tissues and that this ratio is important
in regulating the differentiation of these
tissues. ±or example, Dsg1 is expressed in
all layers of the stratiFed epithelial layers of
the skin, whereas Dsg3 is expressed only
in the suprabasal layer. In contrast, Dsg1
and Dsg3 are expressed in all cell layers of
the stratiFed epithelia of the oral mucosa.
Using a transgenic approach, Dsg3 was
expressed in all epithelial cell layers of the
mouse skin producing a Dsg1 : Dsg3 ratio
similar to that in the oral mucosa. Interest-
ingly, the stratum corneum, the outermost
layer of the skin of these transgenic mice,
now had a histological appearance similar
to that of the oral mucosa. ±urthermore,
the skin of these mice had excessive
transepidermal water loss that resulted in
death due to dehydration, indicating that
the Dsg3/Dsg1 ratio is also important in
the regulation of barrier function.
Tight Junctions
Tight junctions form a meshwork of inter-
connected strands grouped in a narrow
belt at the apical region of epithelial
or endothelial cell–cell adhesion. These
structures have been studied primarily in
epithelial cells whose monolayers form vi-
tal cell barriers that tightly regulate the
movement of fluid and molecules between
different tissue compartments. In addi-
tion to regulating paracellular transport,
TJs separate the apical plasma membrane
from the basal plasma membrane, and
thus act as a fence to maintain the dif-
ferent lipid and protein compositions of
these two cell surfaces. At the ultrastruc-
tural level, the plasma membranes of two
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