Rare Diseases Symptoms Automatic Extraction
Home
A random Abstract
Our Project
Our Team
Functional rescue of Kallmann syndrome-associated prokineticin receptor 2 (PKR2) mutants deficient in trafficking.
[kallmann syndrome]
Mutations
in
the
G
protein-coupled
prokineticin
receptor
2
(
PKR
2
)
are
known
to
cause
Kallmann
syndrome
and
idiopathic
hypogonadotropic
hypogonadism
manifesting
with
delayed
puberty
and
infertility
.
Some
of
the
mutant
receptors
are
not
routed
to
the
cell
surface
;
instead
,
they
are
trapped
in
the
cellular
secretory
pathway
.
The
cell-permeant
agonists
/
antagonists
have
been
used
to
rescue
some
membrane
receptors
that
are
not
targeted
onto
the
cell
membrane
.
Here
,
we
chose
three
disease-associated
mutations
(
W
178
S
,
G
234
D
,
and
P
290
S
)
,
which
all
resulted
in
retention
of
PKR
2
intracellularly
.
We
show
that
a
small
molecule
PKR
2
antagonist
(
A
457
)
dramatically
increased
cell
surface
expression
and
rescued
the
function
of
P
290
S
PKR
2
,
but
had
no
effect
on
W
178
S
and
G
234
D
PKR
2
.
Furthermore
,
we
also
tested
chemical
chaperone
glycerol
on
the
cell
surface
expression
and
function
of
PKR
2
mutants
.
Treatment
with
10
%
glycerol
significantly
increased
the
cell
surface
expression
and
signaling
of
P
290
S
and
W
178
S
PKR
2
.
These
data
demonstrate
that
some
Kallmann
syndrome
-associated
,
intracellularly
retained
mutant
PKR
2
receptors
can
be
functionally
rescued
,
suggesting
a
potential
treatment
strategy
for
patients
bearing
such
mutations
.
Diseases
Validation
Diseases presenting
"also tested chemical chaperone glycerol on the cell surface expression"
symptom
kallmann syndrome
You can validate or delete this automatically detected symptom
Validate the Symptom
Delete the Symptom