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Cortactin scaffolds Arp2/3 and WAVE2 at the epithelial zonula adherens.
[wiskott-aldrich syndrome]
Cadherin
junctions
arise
from
the
integrated
action
of
cell
adhesion
,
signaling
,
and
the
cytoskeleton
.
At
the
zonula
adherens
(
ZA
)
,
a
WAVE
2
-
Arp
2
/
3
actin
nucleation
apparatus
is
necessary
for
junctional
tension
and
integrity
.
But
how
this
is
coordinated
with
cadherin
adhesion
is
not
known
.
We
now
identify
cortactin
as
a
key
scaffold
for
actin
regulation
at
the
ZA
,
which
localizes
to
the
ZA
through
influences
from
both
E
-
cadherin
and
N-WASP
.
Using
cell-free
protein
expression
and
fluorescent
single
molecule
coincidence
assays
,
we
demonstrate
that
cortactin
binds
directly
to
the
cadherin
cytoplasmic
tail
.
However
,
its
concentration
with
cadherin
at
the
apical
ZA
also
requires
N-WASP
.
Cortactin
is
known
to
bind
Arp
2
/
3
directly
(
Weed
,
S
.
A
.
,
Karginov
,
A
.
V
.
,
Schafer
,
D
.
A
.
,
Weaver
,
A
.
M
.
,
Kinley
,
A
.
W
.
,
Cooper
,
J
.
A
.
,
and
Parsons
,
J
.
T
.
(
2000
)
J
.
Cell
Biol
.
151
,
29
-
40
)
.
We
further
show
that
cortactin
can
directly
bind
WAVE
2
,
as
well
as
Arp
2
/
3
,
and
both
these
interactions
are
necessary
for
actin
assembly
at
the
ZA
.
We
propose
that
cortactin
serves
as
a
platform
that
integrates
regulators
of
junctional
actin
assembly
at
the
ZA
.
Diseases
Validation
Diseases presenting
"single molecule coincidence assays"
symptom
wiskott-aldrich syndrome
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