Insights into the Role of Cell–Cell Junctions in Physiology and Disease - International Review of Cell and Molecular Biology - page 186

of in vitro methods and results that shed light on the intricacy of these fasci-
nating proteins. Given the overwhelming amount of work done in this area,
we restrict ourselves to certain key findings and emphasize that omission of
certain findings should not be taken to signify a lack of importance. As a mat-
ter of simplifying nomenclature, we let “junctions” and “interactions” refer
to cell-cell versions for the rest of this chapter, unless otherwise stated.
2. THE STRUCTURE AND COMPOSITION OF CELL
JUNCTIONS
2.1. Overview of cell junctions
Both cell-cell and cell-matrix adhesions are vital for the formation, compo-
sition, architecture, and function of tissues. However, significant pathways
involved in tissue integrity and function are determined to a large part by
adhesion and communication between individual cells, which are in turn
mediated by cell junctions ( Kobielak and Fuchs, 2006 ). Recent studies pro-
vided much insight into the molecular composition and structure of cell
junctions, and investigators are starting to understand the underlying mech-
anisms of their diverse functions. In vertebrates, cell-cell junctions can be
classified into four functional classes: (1) adherens junctions and (2) desmo-
somes, which mechanically link cells by bridging the cytoskeleton of adja-
cent cells, (3) communicating junctions, or gap junctions , which chemically
and electrically couple neighboring cells, and (4) occluding junctions, or
tight junctions , which are essential for establishing barrier function across a cell
layer ( Fig. 5.1 ). Sometimes, the adherens junctions and desmosomes are
grouped into what are called anchoring junctions, but for this chapter, they
are left separate. Working together, these four-cell junctional classes play
vital roles in development, health, and disease ( Holen et al., 2012 ).
2.2. Adherens junctions
The adherens junctions are calcium-dependent (cadherin-based) anchoring
junctions. The structure of adherens junctions derives from three main func-
tional families. The (i) classical cadherins (such as E-, N-, P-, and
VE-cadherin) are transmembrane proteins that form homodimers with
cadherins from adjacent cells and whose intracellular tails provide a scaffold
for the (ii) armadillo family members (such as b -catenin, plakoglobin/
g -catenin, and p120-catenin), which bind the cadherin tails and anchor
(iii) cytoskeletal adapter proteins (such as a -catenin), which in turn anchor
the adherens junctions to the cytoskeleton ( Green et al., 2010; Meng and