Cell Junctions, Structure, Function, and Regulation
331
provide the physical link at cell–matrix
junctions.
1.3
Integrins
1.3.1
The Integrin Family
Integrins comprise a large family of cell
surface proteins. They are heterodimeric
transmembrane receptors for ECM pro-
teins (Fig. 2). Each integrin contains one
α
-subunit and one
β
-subunit. Both
α
-
and
β
-subunits pass through the plasma
membrane, and each subunit contains a
relatively large extracellular segment with
a globular ligand-binding domain. Most
α
-and
β
-subunits also contain relatively
small intracellular domains (cytoplasmic
domains or tails) consisting of from 13 to
70 amino acids. The exception is the
β
4
subunit cytoplasmic domain, which con-
tains 1000 amino acids.
Integrins are highly evolutionarily con-
served. Integrin homologs have been iden-
ti±ed in all metazoans from flies and
nematodes to humans. In mammals, there
are currently 8 known
β
-subunits and 18
α
-subunits that heterodimerize in differ-
ent combinations to generate 24 distinct
integrin heterodimers (Table 4). Several
integrin subunits can be modi±ed by al-
ternative splicing, further adding to the
complexity of the integrin family. The spe-
ci±c combination of
α
-and
β
-subunits de-
termines ligand-binding speci±city. Some
integrins are speci±c for a single compo-
nent of the ECM, such as the
α
5
β
1
integrin
that binds only to ±bronectin. Most inte-
grin heterodimers can bind to more than
one extracellular matrix component. The
α
v
β
3
integrin is one of the more promis-
cuous integrins; it binds to vitronectin,
±bronectin, and ±brinogen, among other
ECM components.
Most
cells
express
several
different
integrin heterodimers allowing them to
interact with multiple components of the
ECM, and a cell’s integrin repertoire can
be regulated both developmentally and in
response to changes in the physiological
environment.
Although
most
integrin
heterodimers are expressed by a variety
of cell types, some integrins are expressed
in a cell-type speci±c manner. The
α
IIb
β
3
integrin is expressed only in platelets. The
α
7
β
1
integrin is expressed exclusively in
neuronal cells and integrins containing the
β
2
subunit are expressed only by immune
cells also referred to as leukocytes.
The identi±cation of human hereditary
diseases involving mutations in genes en-
coding integrins, and the analysis of null
mutations in integrin genes in mice have
underscored the importance of integrin
receptors in physiological and develop-
mental processes. To date there are four
inherited disorders involving integrins.
Leukocyte adhesion de±ciency-1 (LAD1)
is caused by mutations in the integrin
β
2
subunit where affected individuals show
Fig. 2
Integrin heterodimer. Shown is a
schematic representation of an integrin
heterodimer. The typical small
cytoplasmic domains and large
extracellular domains of the
α
-and
β
-subunits are indicated by brackets.
The N-terminal globular domains of the
α
-and
β
-subunits that function in ligand
binding are indicated by a dashed box.
Plasma membrane
Extracellular domains
Cytoplasmic domains
ECM ligand
ab
previous page 1005 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online next page 1007 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online Home Toggle text on/off