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Teneurin-4 promotes cellular protrusion formation and neurite outgrowth through focal adhesion kinase signaling.
[wiskott-aldrich syndrome]
Teneurin-
4
(
Ten
-
4
)
,
a
transmembrane
protein
,
is
highly
expressed
in
the
central
nervous
system
;
however
,
its
cellular
and
molecular
function
in
neuronal
differentiation
remains
unknown
.
In
this
study
,
we
aimed
to
elucidate
the
function
of
Ten
-
4
in
neurite
outgrowth
.
Ten
-
4
expression
was
induced
during
neurite
outgrowth
of
the
neuroblastoma
cell
line
Neuro-
2
a
.
Ten
-
4
protein
was
localized
at
the
neurite
growth
cones
.
Knockdown
of
Ten
-
4
expression
in
Neuro-
2
a
cells
decreased
the
formation
of
the
filopodia-like
protrusions
and
the
length
of
individual
neurites
.
Conversely
,
overexpression
of
Ten
-
4
promoted
filopodia-like
protrusion
formation
.
In
addition
,
knockdown
and
overexpression
of
Ten
-
4
reduced
and
elevated
the
activation
of
focal
adhesion
kinase
(
FAK
)
and
Rho-family
small
GTPases
,
Cdc
42
and
Rac
1
,
key
molecules
for
the
membranous
protrusion
formation
downstream
of
FAK
,
respectively
.
Inhibition
of
the
activation
of
FAK
and
neural
Wiskott-
Aldrich
syndrome
protein
(
N-WASP
)
,
which
is
a
downstream
regulator
of
FAK
and
Cdc
42
,
blocked
protrusion
formation
by
Ten
-
4
overexpression
.
Further
,
Ten
-
4
colocalized
with
phosphorylated
FAK
in
the
filopodia-like
protrusion
regions
.
Together
,
our
findings
show
that
Ten
-
4
is
a
novel
positive
regulator
of
cellular
protrusion
formation
and
neurite
outgrowth
through
the
FAK
signaling
pathway
.
Diseases
Validation
Diseases presenting
"positive regulator"
symptom
aromatase deficiency
familial mediterranean fever
wiskott-aldrich syndrome
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