Rare Diseases Symptoms Automatic Extraction
Home
A random Abstract
Our Project
Our Team
RhoA activation by CNFy restores cell-cell adhesion in kindlin-2-deficient keratinocytes.
[kindler syndrome]
Kindlins
are
a
family
of
integrin
adapter
and
cell-matrix
adhesion
proteins
causally
linked
to
human
genetic
disorders
.
Kindlin-
2
is
a
ubiquitously
expressed
protein
with
manifold
functions
and
interactions
.
The
contribution
of
kindlin-
2
to
integrin-based
cell-matrix
adhesions
has
been
extensively
explored
,
while
other
integrin-independent
roles
emerge
.
Because
of
the
early
involvement
of
kindlin-
2
in
development
,
no
viable
animal
models
with
its
constitutional
knockout
are
available
to
study
its
physiological
functions
in
adult
skin
.
Here
,
we
uncovered
a
critical
physiological
role
of
kindlin-
2
in
the
epidermis
by
using
a
skin
-equivalent
model
with
shRNA-mediated
knock-down
of
kindlin-
2
in
keratinocytes
.
Kindlin-
2
-
deficient
keratinocytes
built
stratified
epidermal
layers
,
but
displayed
impaired
dermal-epidermal
and
intra-epidermal
adhesion
and
barrier
function
.
Co
-immunoprecipitation
studies
demonstrated
that
kindlin-
2
interacts
with
both
integrin-
and
cadherin-based
adhesions
.
In
kindlin-
2
-
deficient
keratinocytes
,
reduced
cell-cell
adhesion
was
associated
with
abnormal
cytoplasmic
distribution
of
adherens
junctions
and
desmosomal
proteins
,
which
was
dependent
on
RhoA
activation
.
Direct
activation
of
RhoA
with
recombinant
bacterial
cytotoxic
necrotizing
factor
y
(
CNFy
)
reverted
the
abnormal
phenotype
and
barrier
function
of
kindlin-
2
-
deficient
keratinocytes
and
skin
equivalents
.
These
findings
have
physiological
and
pathological
significance
,
since
kindlin-
2
expression
modulates
the
phenotype
in
Kindler
syndrome
,
a
skin
fragility
disorder
caused
by
kindlin-
1
deficiency
.
Our
results
suggest
that
pharmacological
regulation
of
RhoGTPase
activity
may
represent
a
therapeutic
option
for
skin
fragility
.
Diseases
Validation
Diseases presenting
"reduced cell-cell adhesion was associated with abnormal cytoplasmic distribution of adherens junctions and desmosomal proteins"
symptom
kindler syndrome
You can validate or delete this automatically detected symptom
Validate the Symptom
Delete the Symptom