The small GTPase MRAS is a broken switch
Nature Communications,
Год журнала:
2025,
Номер
16(1)
Опубликована: Янв. 14, 2025
Intense
research
on
founding
members
of
the
RAS
superfamily
has
defined
our
understanding
these
critical
signalling
proteins,
leading
to
premise
that
small
GTPases
function
as
molecular
switches
dependent
differential
nucleotide
loading.
The
closest
homologs
H/K/NRAS
are
three-member
RRAS
family,
and
interest
in
MRAS
GTPase
a
regulator
MAPK
activity
recently
intensified.
We
show
here
does
not
classical
switch
is
unable
exchange
GDP-to-GTP
solution
or
when
tethered
lipid
bilayer.
defect
unaffected
by
inclusion
GEF
SOS1
conserved
distal
ortholog
from
nematodes.
Synthetic
activating
mutations
widely
used
study
presumed
GTP-loaded
state
do
increase
exchange,
but
instead
drive
effector
binding
due
sampling
an
activated
conformation
GDP-loaded
state.
This
includes
nucleation
SHOC2-PP1Cα
holophosphatase
complex.
Acquisition
NMR
spectra
isotopically
labeled
live
cells
validated
remains
fully
GDP-loaded,
even
supposed
mutant.
These
data
GTPases,
including
those
most
similar
KRAS,
have
disparate
biochemical
activities
challenge
current
dogma
MRAS,
suggesting
previous
may
need
reinterpretation.
Small
family
classically
switches,
adopting
off
conformations
bound
nucleotides.
Here
authors
reveal
closely
related
archetypal
RAS,
completely
deficient
GTP
exchange.
Язык: Английский
The PACT Network: PRL, ARL, CNNM, and TRPM Proteins in Magnesium Transport and Disease
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(4), С. 1528 - 1528
Опубликована: Фев. 12, 2025
Magnesium,
the
most
abundant
divalent
metal
within
cell,
is
essential
for
physiological
function
and
critical
in
cellular
signaling.
To
maintain
homeostasis,
intracellular
magnesium
levels
are
tightly
regulated,
as
dysregulation
linked
to
numerous
diseases,
including
cancer,
diabetes,
cardiovascular
disorders,
neurological
conditions.
Over
past
two
decades,
extensive
research
on
magnesium-regulating
proteins
has
provided
valuable
insight
into
their
pathogenic
therapeutic
potential.
This
review
explores
an
emerging
mechanism
of
homeostasis
involving
PRL
(phosphatase
regenerating
liver),
ARL
(ADP
ribosylation
factor-like
GTPase
family),
CNNM
(cyclin
cystathionine
β-synthase
domain
transport
mediator),
TRPM
(transient
receptor
potential
melastatin)
families,
collectively
termed
herein
PACT
network.
While
each
protein
been
studied
its
individual
signaling
disease
contexts,
interactions
suggest
a
broader
regulatory
network
with
consolidates
current
knowledge
proteins'
structure,
function,
identifies
gaps
encourage
future
investigation.
As
field
continues
advance,
understanding
offers
new
opportunities
basic
development
targeting
magnesium-related
disorders.
Язык: Английский
ER nests are specialized ER subdomains in Arabidopsis where peroxisomes and lipid droplets form
Developmental Cell,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 1, 2025
Язык: Английский
Announcing the JCS–David Stephens Prize and the 2024 winner Anja Konietzny
Journal of Cell Science,
Год журнала:
2025,
Номер
138(7)
Опубликована: Апрель 1, 2025
Язык: Английский
Mapping the MOB proteins’ proximity network reveals a unique interaction between human MOB3C and the RNase P complex
Journal of Biological Chemistry,
Год журнала:
2023,
Номер
299(9), С. 105123 - 105123
Опубликована: Авг. 1, 2023
Distinct
functions
mediated
by
members
of
the
monopolar
spindle-one-binder
(MOB)
family
proteins
remain
elusive
beyond
evolutionarily
conserved
and
well-established
roles
MOB1
(MOB1A/B)
in
regulating
tissue
homeostasis
within
Hippo
pathway.
Since
MOB
are
adaptors,
understanding
how
they
engage
protein-protein
interactions
help
assemble
complexes
is
essential
to
define
full
scope
their
biological
functions.
To
address
this,
we
undertook
a
proximity-dependent
biotin
identification
approach
interactomes
all
seven
human
HeLa
embryonic
kidney
293
cell
lines.
We
uncovered
>200
interactions,
which
at
least
70%
unreported
on
BioGrid.
The
generated
dataset
reliably
recalled
bona
fide
interactors
well-studied
MOBs.
further
defined
common
differential
interactome
between
different
MOBs
subfamily
an
individual
level.
discovered
unique
association
MOB3C
7
10
protein
subunits
RNase
P
complex,
endonuclease
that
catalyzes
tRNA
5'
maturation.
As
proof
principle
for
robustness
dataset,
validated
specific
interaction
with
catalytically
active
using
affinity
purification-mass
spectrometry
pre-tRNA
cleavage
assays
pulldowns.
In
summary,
our
data
provide
novel
insights
into
biology
reveal
first
MOB3C,
components
hence
exciting
nexus
RNA
biology.
Язык: Английский
The ARF GTPase regulatory network in collective invasion and metastasis
Biochemical Society Transactions,
Год журнала:
2023,
Номер
51(4), С. 1559 - 1569
Опубликована: Авг. 25, 2023
The
ability
to
remodel
and
move
cellular
membranes,
the
cargoes
regulated
by
these
allows
for
specialised
functions
occur
in
distinct
regions
of
cell
a
process
known
as
polarisation.
collectively
co-ordinate
such
polarisation
between
cells
genesis
multicellularity,
formation
organs.
During
tumourigenesis,
rules
tissue
become
dysregulated,
allowing
collective
polarity
rearrangements
that
can
drive
metastasis.
In
this
review,
we
focus
on
how
membrane
trafficking
underpins
invasion
metastasis
cancer.
We
examine
through
lens
ADP-ribosylation
factor
(ARF)
subfamily
small
GTPases,
focusing
ARF
regulatory
network
-
activators,
inactivators,
effectors,
modifications
controls
GTPase
function.
Язык: Английский
First person – Laura Quirion
Journal of Cell Science,
Год журнала:
2024,
Номер
137(9)
Опубликована: Май 1, 2024
ABSTRACT
First
Person
is
a
series
of
interviews
with
the
first
authors
selection
papers
published
in
Journal
Cell
Science,
helping
researchers
promote
themselves
alongside
their
papers.
Laura
Quirion
author
on
‘
Mapping
global
interactome
ARF
family
reveals
spatial
organization
cellular
signaling
pathways’,
JCS.
PhD
candidate
lab
Jean-François
Côté
at
Montreal
Clinical
Research
Institute,
Montréal,
Canada,
investigating
dynamics
GTPase
signaling.
Язык: Английский
SNX5-Rab11a protects against cardiac hypertrophy through regulating LRP6 membrane translocation
Journal of Molecular and Cellular Cardiology,
Год журнала:
2024,
Номер
194, С. 46 - 58
Опубликована: Июнь 29, 2024
Язык: Английский
A Proximity MAP of RAB GTPases
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 6, 2024
ABSTRACT
RAB
GTPases
are
the
most
abundant
family
of
small
and
regulate
multiple
aspects
membrane
trafficking
events,
from
cargo
sorting
to
vesicle
budding,
transport,
docking,
fusion.
To
these
processes,
RABs
tightly
regulated
by
guanine
exchange
factors
(GEFs)
GTPase-activating
proteins
(GAPs).
Activated
recruit
effector
that
trafficking.
Identifying
RAB-associated
has
proven
be
difficult
because
their
association
with
interacting
is
often
transient.
Recent
advances
in
proximity
labeling
approaches
allow
for
covalent
neighbors
interest
now
permit
cataloging
vicinity
GTPases.
Here,
we
report
APEX2
23
human
neighboring
proteomes.
We
have
used
bioinformatic
analyses
map
specific
proximal
an
extensive
array
GTPases,
localization
can
inferred
adjacent
proteins.
Focusing
on
examples,
identified
a
physical
interaction
between
RAB25
DENND6A,
which
affects
cell
migration.
also
show
functional
relationships
RAB14
EARP
complex,
or
SHIP164
its
close
ortholog
UHRF1BP1.
Our
dataset
provides
resource
community
helps
define
novel
connections
Язык: Английский