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Kindlins: essential regulators of integrin signalling and cell-matrix adhesion.
[kindler syndrome]
Integrin-mediated
cell-
ECM
(
extracellular
matrix
)
adhesion
is
a
fundamental
process
that
controls
cell
behaviour
.
For
correct
cell-
ECM
adhesion
,
both
the
ligand-binding
affinity
and
the
spatial
organization
of
integrins
must
be
precisely
controlled
;
how
integrins
are
regulated
,
however
,
is
not
completely
understood
.
Kindlins
constitute
a
family
of
evolutionarily
conserved
cytoplasmic
components
of
cell-
ECM
adhesions
that
bind
to
beta
-integrin
cytoplasmic
tails
directly
and
cooperate
with
talin
in
integrin
activation
.
In
addition
,
kindlins
interact
with
many
components
of
cell-
ECM
adhesions--such
as
migfilin
and
integrin-linked
kinase
--
to
promote
cytoskeletal
reorganization
.
Loss
of
kindlins
causes
severe
defects
in
integrin
signalling
,
cell-
ECM
adhesion
and
cytoskeletal
organization
,
resulting
in
early
embryonic
lethality
(
kindlin-
2
)
,
postnatal
lethality
(
kindlin-
3
)
and
Kindler
syndrome
(
kindlin-
1
)
.
It
is
therefore
clear
that
kindlins
,
together
with
several
other
integrin-
proximal
proteins
,
are
essential
for
integrin
signalling
and
cell-
ECM
adhesion
regulation
.
Diseases
Validation
Diseases presenting
"severe defects in integrin"
symptom
kindler syndrome
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