332
Cell Junctions, Structure, Function, and Regulation
Tab. 4
Integrins and their ligands.
(Adapted from Table 1 in van der Flier, A.,
Sonnenberg, A. (2001) Function and
interactions of integrins, Cell Tissue Res.
305
, 285–298).
Integrin
Ligand
a
(ECM, soluble,
counter receptors)
α
1
β
1
Co, Ln
2
α
2
β
1
Co, Ln
α
3
β
1
Ln
α
4
β
1
Fn, VCAM
α
4
β
7
Fn, VCAM, MadCAM
α
5
β
1
Fn
α
6
β
1
Ln
α
6
β
4
Ln
α
7
β
1
Ln
α
8
β
1
Fn, Tn, VCAM
α
9
β
1
Tn, Co, Ln, VCAM
α
10
β
1
Co
α
11
β
1
Co
α
v
β
1
Fn, Vn
α
v
β
3
Vn, Fn, vWF, Op, Tn
α
v
β
5
Vn
α
v
β
6
Fn, Tn
α
v
β
8
Co, Ln, Fn
α
IIb
β
3
Vn, Fn, vWF, Fg, Fg
α
L
β
2
ICAM 1–5
α
M
β
2
Fg, iC3b, ICAM
α
x
β
2
Fg, iC3b
α
D
β
2
ICAM, VAM
α
E
β
7
E-cadherin
a
ECM, soluble, and counter receptors
ligands are shown in red, blue, and green,
respectively.
severe defciencies in their immune re-
sponses. Glanzmann’s thrombasthenia,
a bleeding disorder, is caused by mu-
tations that prevent the proper expres-
sion oF the
α
IIb
β
3
platelet integrin and
some mild Forms oF muscular dystro-
phy are associated with mutations in the
α
7
subunit, which aFFect the Function oF
the
α
7
β
1
laminin binding integrin. Ad-
ditionally, mutations that inhibit
α
6
β
4
Function result in a skin blistering dis-
order (see Sect. 1.5). These phenotypes are
recapitulated in mice carrying the cor-
responding homozygous null mutations
in genes encoding the
β
2
IIb
3
7
6
,
and
β
4
integrin subunits.
The generation oF targeted deletions
in integrin genes in mice has probably
provided the most insight into the de-
velopmental role oF individual integrin
heterodimers. Homozygous null muta-
tions in the gene encoding the integrin
β
1
subunit gene result in early embryonic
lethality with deFects in implantation and
gastrulation. Targeted deletion oF the inte-
grins
α
5
and
α
4
subunit genes also result in
embryonic lethality. The
α
5
-null embryos
have deFects in vascular and mesoderm de-
velopment, whereas
α
4
-null embryos show
deFects in heart development. Deletion oF
the integrin
α
8
subunit gene results in de-
Fects in kidney development and deletion
oF the integrin
α
9
subunit results in de-
Fects in the development oF the lymphatics
and thoracic duct. The
α
9
-null mice die
several days aFter birth From respiratory
Failure due to fluid accumulation. Mice
with null mutations in the integrin
α
3
subunit gene show abnormalities in kid-
ney and lung development and also have
a skin blistering phenotype. Interestingly,
null mutations in some integrin genes
do not produce obvious developmental
phenotypes. However, in some instances,
phenotypes are observed in adult animals
when challenged or stressed in some way.
±or example, mice with null mutations in
the integrin
β
6
subunit gene are viable and
Fertile but show increased skin and lung
inflammation in response to environmen-
tal triggers.
1.3.2
Integrin Ligands
In addition to ECM ligands, some in-
tegrins have soluble ligands, and other
integrins bind to cell surFace receptors
(counterreceptors) on neighboring cells
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