Insights into the Role of Cell–Cell Junctions in Physiology and Disease - International Review of Cell and Molecular Biology - page 188

biology processes, such as cell proliferation and cancer ( Lie et al., 2005;
Peifer et al., 1991 ). Moreover, recent evidence suggests that tethering the
actin cytoskeleton is essential for adherens junctions' structural and signaling
functions ( Jamora and Fuchs, 2002 ).
2.3. Desmosomes
As another group of cadherin-based anchoring junctions, desmosomes are
considered particularly important for maintaining the overall integrity of tis-
sues, including epidermal and myocardial tissues ( Green and Simpson, 2007;
Stokes, 2007 ). Morphologically, desmosomes have a characteristic and
highly organized structure. They form a symmetrical, disc-shaped,
electron-dense plaque consisting of an outer dense plaque and an inner dense
plaque ( North et al., 1999 ). Just like adherens junctions, desmosomes can be
broken down into three major components: (nonclassical) cadherins
(desmocollin and desmoglein), armadillo proteins (plakoglobin and
plakophilin), and a (cytoskeletal-linking) plakin (desmoplakin) ( Getsios
et al., 2004 ). Of these five major desmosomal proteins, heterophilic inter-
actions between desmocollin and desmoglein mediate direct intercellular
communication ( Runswick et al., 2001; Tselepis et al., 1998 ). Plakoglobin,
which will be referenced repeatedly in this chapter, is notable for being the
only known constituent common to desmosomes and adherens junctions
( Cowin et al., 1986 ).
One key function of desmosomes is regulating the development and
maintenance of strong intercellular adhesion. The linkage of the
desmosome-intermediate filament network contributes to the formation
of a “scaffolding” effect, which distributes mechanical stresses throughout
tissues ( Huen et al., 2002 ). It is thus expected that mutations in genes
encoding desmosomal proteins can lead to diseases with altered intercellular
adhesion and subsequently, diminished tissue integrity. In support of this,
many desmosomal-related conditions appear in cardiac and dermal tissues,
which are subjected to constant mechanical stress ( Brooke et al., 2012 ).
Some recent evidence attributes the characteristic “superglue” function of
desmosomes to its ability to adopt a strongly adhesive state known as “hyp-
eradhesion” ( Cirillo et al., 2010; Garrod and Kimura, 2008 ). Other than
intercellular adhesion, recent work has emphasized the multiple critical roles
that desmosomal proteins play in regulating the various facets of develop-
ment, life, and disease, some of which will be covered later.