326
Cell Junctions, Structure, Function, and Regulation
Important insights have also been gleaned from gene knockout studies, which have
identiFed critical roles for many components of these adhesion complexes during
development. Mutations in protein components of these adhesion complexes have
also been identiFed in the etiology of a variety of human diseases.
1
Cell–matrix Adhesion
1.1
Overview
The adhesion of cells to
extracellular
matrix (ECM) proteins is essential for
embryonic development, tissue morpho-
genesis, and homeostasis of all vertebrate
organisms. Integrins comprise the major
class of cell surface proteins that bind
to ECM proteins. Integrins contribute to
tissue structure by forming transmem-
brane links between ECM proteins and
the cell’s cytoskeleton at sites referred
to as cell–matrix junctions. The best-
characterized cell–matrix junctions are
focal adhesions and hemidesmosomes.
At focal adhesions, integrins connect the
ECM with the actin microFlament cy-
toskeleton, and at hemidesmosomes in-
tegrins connect the ECM with the inter-
mediate Flament cytoskeleton. Integrins
are also signaling receptors, providing
cells with information to evaluate the
composition and physical state of their en-
vironment. Integrin signaling contributes
to the regulation of cell migration, cell
proliferation, survival and differentiation.
Important insights into the physiological
roles of extracellular matrix proteins and
their integrin receptors has been gained
from cell culture models, gene knockout
approaches in mice, and the analysis of hu-
man hereditary disorders involving genes
encoding cell adhesion proteins.
1.2
Extracellular Matrix
The extracellular matrix (ECM) is com-
prised of cell-secreted macromolecules
that form an insoluble meshwork outside
cells. The ECM holds cells together in tis-
sues, and tissues together in organs. Large
glycoproteins such as collagens, laminins,
and Fbronectin are important components
of the ECM. They contribute to the physical
characteristics of the ECM and function as
adhesive ligands for cells. Also important
to the structure of the ECM are the long,
unbranched, charged polysaccharides re-
ferred to as glycosaminoglycans (GAGs)
and proteins containing GAG chains called
proteoglycans. Because of their extended
and charged nature, GAGs easily form hy-
drated gels that are important for tissues
to resist compressive forces.
ECM is the major component in con-
nective tissue, such as skin, bone, and
cartilage. The ECM is secreted and or-
ganized by cells that reside within the
connective tissue: Fbroblasts in the con-
nective tissue in skin, chondrocytes in
cartilage, and osteoblasts in bone. Other
cells such as epithelial cells, endothelial
cells, and nerve cells secrete ECM pro-
teins that become assembled into a basal
lamina or basement membrane (±ig. 1).
Unlike the ECM of connective tissue,
which surrounds the cells that secrete it,
the basement membrane is found only
on the basal cell surface of endothelial
and epithelial cells. Basement membranes
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