Rare Diseases Symptoms Automatic Extraction
Home
A random Abstract
Our Project
Our Team
Kindlin-1 Is required for RhoGTPase-mediated lamellipodia formation in keratinocytes.
[kindler syndrome]
Kindlin-
1
is
an
epithelial-
specific
member
of
the
novel
kindlin
protein
family
,
which
are
regulators
of
integrin
functions
.
Mutations
in
the
gene
that
encodes
Kindlin-
1
,
FERMT
1
(
KIND
1
)
,
cause
the
Kindler
syndrome
(
KS
)
,
a
human
disorder
characterized
by
mucocutaneous
fragility
,
progressive
skin
atrophy
,
ulcerative
colitis
,
photosensitivity
,
and
propensity
to
skin
cancer
.
Our
previous
studies
indicated
that
loss
of
kindlin-
1
resulted
in
abnormalities
associated
with
integrin
functions
,
such
as
adhesion
,
proliferation
,
polarization
,
and
motility
of
epidermal
cells
.
Here
,
we
disclosed
novel
FERMT
1
mutations
in
KS
and
used
them
,
in
combination
with
small
-interfering
RNA
,
protein
,
and
imaging
studies
,
to
uncover
new
functions
for
kindlin-
1
in
keratinocytes
and
to
discern
the
molecular
pathology
of
KS
.
We
show
that
kindlin-
1
forms
molecular
complexes
with
beta
1
integrin
,
alpha-actinin
,
migfilin
,
and
focal
adhesion
kinase
and
regulates
cell
shape
and
migration
by
controlling
lamellipodia
formation
.
Kindlin-
1
governs
these
processes
by
signaling
via
Rho
family
GTPases
,
and
it
is
required
to
maintain
the
pool
of
GTP-bound
,
active
Rac
1
,
RhoA
and
Cdc
42
,
and
the
phosphorylation
of
their
downstream
effectors
p
21
-
activated
kinase
1
,
LIM
kinase
,
and
cofilin
.
Loss
of
these
kindlin-
1
functions
forms
the
biological
basis
for
the
epithelial
cell
fragility
and
atrophy
in
the
pathology
of
KS
.
Diseases
Validation
Diseases presenting
"and propensity to skin cancer"
symptom
kindler syndrome
You can validate or delete this automatically detected symptom
Validate the Symptom
Delete the Symptom