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Lamellipodin and the Scar/WAVE complex cooperate to promote cell migration in vivo.
[wiskott-aldrich syndrome]
Cell
migration
is
essential
for
development
,
but
its
deregulation
causes
metastasis
.
The
Scar
/
WAVE
complex
is
absolutely
required
for
lamellipodia
and
is
a
key
effector
in
cell
migration
,
but
its
regulation
in
vivo
is
enigmatic
.
Lamellipodin
(
Lpd
)
controls
lamellipodium
formation
through
an
unknown
mechanism
.
Here
,
we
report
that
Lpd
directly
binds
active
Rac
,
which
regulates
a
direct
interaction
between
Lpd
and
the
Scar
/
WAVE
complex
via
Abi
.
Consequently
,
Lpd
controls
lamellipodium
size
,
cell
migration
speed
,
and
persistence
via
Scar
/
WAVE
in
vitro
.
Moreover
,
Lpd
knockout
mice
display
defective
pigmentation
because
fewer
migrating
neural
crest-derived
melanoblasts
reach
their
target
during
development
.
Consistently
,
Lpd
regulates
mesenchymal
neural
crest
cell
migration
cell
autonomously
in
Xenopus
laevis
via
the
Scar
/
WAVE
complex
.
Further
,
Lpd
's
Drosophila
melanogaster
orthologue
Pico
binds
Scar
,
and
both
regulate
collective
epithelial
border
cell
migration
.
Pico
also
controls
directed
cell
protrusions
of
border
cell
clusters
in
a
Scar
-dependent
manner
.
Taken
together
,
Lpd
is
an
essential
,
evolutionary
conserved
regulator
of
the
Scar
/
WAVE
complex
during
cell
migration
in
vivo
.
Diseases
Validation
Diseases presenting
"pigmentation"
symptom
aniridia
congenital adrenal hyperplasia
congenital toxoplasmosis
cushing syndrome
epidermolysis bullosa simplex
erythropoietic protoporphyria
gm1 gangliosidosis
hirschsprung disease
homocystinuria without methylmalonic aciduria
junctional epidermolysis bullosa
kallmann syndrome
kindler syndrome
oculocutaneous albinism
oral submucous fibrosis
phenylketonuria
proteus syndrome
wiskott-aldrich syndrome
This symptom has already been validated