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A random Abstract
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The nuclear pore complex protein ALADIN is mislocalized in triple A syndrome.
[triple a syndrome]
Triple
A
syndrome
is
a
human
autosomal
recessive
disorder
characterized
by
an
unusual
array
of
tissue-
specific
defects
.
Triple
A
syndrome
arises
from
mutations
in
a
WD-repeat
protein
of
unknown
function
called
ALADIN
(
also
termed
Adracalin
or
AAAS
)
.
We
showed
previously
that
ALADIN
localizes
to
nuclear
pore
complexes
(
NPCs
)
,
large
multiprotein
assemblies
that
are
the
sole
sites
of
nucleocytoplasmic
transport
.
Here
,
we
present
evidence
indicating
that
NPC
targeting
is
essential
for
the
function
of
ALADIN
.
Characterization
of
mutant
ALADIN
proteins
from
triple
A
patients
revealed
a
striking
effect
of
these
mutations
on
NPC
targeting
.
A
variety
of
disease-associated
missense
,
nonsense
,
and
frameshift
mutations
failed
to
localize
to
NPCs
and
were
found
predominantly
in
the
cytoplasm
.
Microscopic
analysis
of
cells
from
a
triple
A
patient
revealed
no
morphological
abnormalities
of
the
nuclei
,
nuclear
envelopes
,
or
NPCs
.
Importantly
,
these
findings
indicate
that
defects
in
NPC
function
,
rather
than
structure
,
give
rise
to
triple
A
syndrome
.
We
propose
that
ALADIN
plays
a
cell
type
-
specific
role
in
regulating
nucleocytoplasmic
transport
and
that
this
function
is
essential
for
the
proper
maintenance
andor
development
of
certain
tissues
.
Our
findings
provide
a
foundation
for
understanding
the
molecular
basis
of
triple
A
syndrome
and
may
lead
to
unique
insights
into
the
role
of
nucleocytoplasmic
transport
in
adrenal
function
and
neurodevelopment
.