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The nuclear pore complex protein ALADIN is anchored via NDC1 but not via POM121 and GP210 in the nuclear envelope.
[triple a syndrome]
The
nuclear
pore
complex
(
NPC
)
consists
of
approximately
30
different
proteins
and
provides
the
only
sites
for
macromolecular
transport
between
cytoplasm
and
nucleus
.
ALADIN
was
discovered
as
a
new
member
of
the
NPC
.
Mutations
in
ALADIN
are
known
to
cause
triple
A
syndrome
,
a
rare
autosomal
recessive
disorder
characterized
by
adrenal
insufficiency
,
alacrima
,
and
achalasia
.
The
function
and
exact
location
of
the
nucleoporin
ALADIN
within
the
NPC
multiprotein
complex
is
still
unclear
.
Using
a
siRNA-based
approach
we
downregulated
the
three
known
membrane
integrated
nucleoporins
NDC
1
,
GP
2
10
,
and
POM
121
in
stably
expressing
GFP-ALADIN
HeLa
cells
.
We
identified
NDC
1
but
not
GP
2
10
and
POM
121
as
the
main
anchor
of
ALADIN
within
the
NPC
.
Solely
the
depletion
of
NDC
1
caused
mislocalization
of
ALADIN
.
Vice
versa
,
the
depletion
of
ALADIN
led
also
to
disappearance
of
NDC
1
at
the
NPC
.
However
,
the
downregulation
of
two
further
membrane-integral
nucleoporins
GP
2
10
and
POM
121
had
no
effect
on
ALADIN
localization
.
Furthermore
,
we
could
show
a
direct
association
of
NDC
1
and
ALADIN
in
NPCs
by
fluorescence
resonance
energy
transfer
(
FRET
)
measurements
.
Based
on
our
findings
we
conclude
that
ALADIN
is
anchored
in
the
nuclear
envelope
via
NDC
1
and
that
this
interaction
gets
lost
,
if
ALADIN
is
mutated
.
The
loss
of
integration
of
ALADIN
in
the
NPC
is
a
main
pathogenetic
aspect
for
the
development
of
the
triple
A
syndrome
and
suggests
that
the
interaction
between
ALADIN
and
NDC
1
may
be
involved
in
the
pathogenesis
of
the
disease
.