Cell Junctions, Structure, Function, and Regulation
329
osteogenesis imperfecta
. In its most severe
f
o
rm
,t
h
i
sd
i
s
o
r
d
e
ri
sc
h
a
r
a
c
t
e
r
i
z
e
db
y
brittle bones, abnormal teeth, thin skin,
and weak tendons, which reflects the
wide tissue distribution of type I collagen.
Mutations
in
genes
that
encode
type
II collagen, which is found mostly in
cartilage, are responsible for disorders
referred to as chondrodysplasias. Affected
individuals
can
have
bone
and
joint
deformities.
Mutations
in
genes
that
encode type III collagen affect the integrity
of blood vessels and skin, reflecting the
tissue distribution of type III collagen.
Null mutations in the homologous genes
in mice result in similar phenotypes.
1.2.2
Laminins
Laminins
comprise
a
family
of
high
molecular weight heterotrimers that are
essential components of basement mem-
branes (Table 2). Each laminin contains
one
α
-subunit, one
β
-subunit, and one
γ
-subunit. To date there are Fve known
α
-subunits, three known
β
-subunits, and
three known
γ
-subunits that form 12 dif-
ferent laminin isoforms, each containing
a distinct combination of
α
-,
β
-and
γ
-
subunits that assemble in a cross-like
Tab. 2
Laminins.
Laminins
Chain composition
Laminin 1
α
1
β
1
γ
1
Laminin 2
α
2
β
1
γ
1
Laminin 3
α
1
β
2
γ
1
Laminin 4
α
2
β
2
γ
1
Laminin 5
α
3
β
3
γ
2
Laminin 6
α
3
β
1
γ
1
Laminin 7
α
3
β
2
γ
1
Laminin 8
α
4
β
1
γ
1
Laminin 9
α
4
β
2
γ
1
Laminin 10
α
5
β
1
γ
1
Laminin 11
α
5
β
2
γ
1
Laminin 12
α
2
β
1
γ
3
structure with one coil-coiled domain con-
taining portions of all three subunits. Most
information about the tissue distribution
of individual laminin subunits is known
(Table 3). However, the expression and
function of laminin isoforms in speciFc
tissues has also been established. ±or
example, laminin-1 (
α
1
β
1
γ
1
) expression
is critical for early vertebrate develop-
ment. Laminin-2 (
α
2
β
1
γ
1
) and laminin-4
(
α
2
β
2
γ
1
) play important roles in the de-
velopment and maintenance of muscles
and nerves. Mutations in the gene for the
laminin
α
2
subunit, which is present in
both laminin-2 and laminin-4, cause some
forms of congenital muscular dystrophy
in humans, in which affected individu-
als show both muscular and neurological
defects. Laminin-5 (
α
3
β
3
γ
2
)ispresen
tin
basement membranes of stratiFed epithe-
lia. Epithelial cell adhesion to laminin-5
is required for epithelial tissues to resist
physical stress. Laminin-5 is also dis-
cussed in Sect. 1.5, because of its central
role in cell–matrix junctions known as
hemidesmosomes. Laminins also play a
critical role in the kidney where laminin ex-
pression is differentially regulated for kid-
ney development and function. Laminin-1
(
α
1
β
1
γ
1
), laminin-8 (
α
4
β
1
γ
1
) and laminin-
10 (
α
5
β
1
γ
1
) are expressed early in the
formation of the glomerular basement
membrane. These laminins are later re-
placed by laminin-9 (
α
4
β
2
γ
1
) and Fnally by
laminin-11 (
α
5
β
2
γ
1
). Mice with null muta-
tions in the gene encoding the laminin
α
5
subunit lack one or both kidneys. When
one kidney is present in
α
5
laminin-null
mice, this kidney is smaller than normal
and shows defects in glomerulogenesis
and in the glomerular basement mem-
brane. As indicated above, the basement
membrane of kidney glomeruli performs
an important Fltration function, and
β
2
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