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Integrin beta4 regulates migratory behavior of keratinocytes by determining laminin-332 organization.
[junctional epidermolysis bullosa]
Whether
alpha
6
beta
4
integrin
regulates
migration
remains
controversial
.
beta
4
integrin-
deficient
(
JEB
)
keratinocytes
display
aberrant
migration
in
that
they
move
in
circles
,
a
behavior
that
mirrors
the
circular
arrays
of
laminin
(
LM
)
-
332
in
their
matrix
.
In
contrast
,
wild-
type
keratinocytes
and
JEB
keratinocytes
,
induced
to
express
beta
4
integrin
,
assemble
laminin-
332
in
linear
tracks
over
which
they
migrate
.
Moreover
,
laminin-
332
-
dependent
migration
of
JEB
keratinocytes
along
linear
tracks
is
restored
when
cells
are
plated
on
wild-
type
keratinocyte
matrix
,
whereas
wild-
type
keratinocytes
show
rotation
over
circular
arrays
of
laminn-
332
in
JEB
keratinocyte
matrix
.
The
activities
of
Rac
1
and
the
actin
cytoskeleton-severing
protein
cofilin
are
low
in
JEB
keratinocytes
compared
with
wild-
type
cells
but
are
rescued
following
expression
of
wild-
type
beta
4
integrin
in
JEB
cells
.
Additionally
,
in
wild-
type
keratinocytes
Rac
1
is
complexed
with
alpha
6
beta
4
integrin
.
Moreover
,
Rac
1
or
cofilin
inactivation
induces
wild-
type
keratinocytes
to
move
in
circles
over
rings
of
laminin-
332
in
their
matrix
.
Together
these
data
indicate
that
laminin-
332
matrix
organization
is
determined
by
the
alpha
6
beta
4
integrin
/
actin
cytoskeleton
via
Rac
1
/
cofilin
signaling
.
Furthermore
,
our
results
imply
that
the
organizational
state
of
laminin-
332
is
a
key
determinant
of
the
motility
behavior
of
keratinocytes
,
an
essential
element
of
skin
wound
healing
and
the
successful
invasion
of
epidermal-derived
tumor
cells
.
Diseases
Validation
Diseases presenting
"type keratinocyte matrix"
symptom
junctional epidermolysis bullosa
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