Trans-Golgi network tethering factors regulate TBK1 trafficking and promote the STING-IFN-I pathway
Cell Discovery,
Год журнала:
2025,
Номер
11(1)
Опубликована: Март 18, 2025
Abstract
The
cGAS-STING
pathway
mediates
the
innate
immune
response
to
cytosolic
DNA,
contributing
surveillance
against
microbial
invasion
or
cellular
damage.
Once
activated,
STING
recruits
TBK1
at
trans-Golgi
network
(TGN),
which
in
turn
phosphorylates
IRF3
induce
type
I
interferon
(IFN-I)
expression.
In
contrast
STING,
little
is
known
about
how
transported
TGN
for
activation.
Here,
we
show
that
multiple
tethering
factors,
a
group
of
proteins
involved
vesicle
capturing,
are
indispensable
STING-IFN-I
signaling.
Deletion
TBC1D23,
recently
reported
factor,
mice
impairs
signaling,
but
with
insignificant
effect
on
STING-NF-κB
Mechanistically,
TBC1D23
interacts
via
WASH
complex
subunit
FAM21
and
promotes
its
endosome-to-TGN
translocation.
Furthermore,
factors
were
reduced
aged
senescent
fibroblasts.
summary,
our
study
uncovers
key
regulators
signaling
suggests
their
reduction
senescence
may
produce
aberrant
Язык: Английский
Recent advances of myotubularin-related (MTMR) protein family in cardiovascular diseases
Frontiers in Cardiovascular Medicine,
Год журнала:
2024,
Номер
11
Опубликована: Март 11, 2024
Belonging
to
a
lipid
phosphatase
family
containing
16
members,
myotubularin-related
proteins
(MTMRs)
are
widely
expressed
in
variety
of
tissues
and
organs.
MTMRs
preferentially
hydrolyzes
phosphatidylinositol
3-monophosphate
(3,5)
bis-phosphate
generate
5-monophosphate,
respectively.
These
phosphoinositides
(PIPs)
promote
membrane
degradation
during
autophagosome-lysosomal
fusion
also
involved
various
regulatory
signal
transduction.
Based
on
the
ability
modulating
levels
these
PIPs,
exert
physiological
functions
such
as
vesicle
trafficking,
cell
proliferation,
differentiation,
necrosis,
cytoskeleton,
migration.
It
has
recently
been
found
that
occurrence
development
several
cardiovascular
diseases,
including
cardiomyocyte
hypertrophy,
proliferation
vascular
smooth
muscle
cell,
LQT1,
aortic
aneurysm,
etc.
This
review
summarizes
highlights
their
pathophysiological
roles
diseases.
Язык: Английский
The emerging role of mtDNA release in sepsis: Current evidence and potential therapeutic targets
Journal of Cellular Physiology,
Год журнала:
2024,
Номер
239(11)
Опубликована: Июнь 18, 2024
Sepsis
is
a
systemic
inflammatory
reaction
caused
by
infection,
and
severe
sepsis
can
develop
into
septic
shock,
eventually
leading
to
multiorgan
dysfunction
even
death.
In
recent
years,
studies
have
shown
that
mitochondrial
damage
closely
related
the
occurrence
development
of
sepsis.
Recent
years
seen
surge
in
concern
over
DNA
(mtDNA),
as
anomalies
this
material
lead
cellular
dysfunction,
disruption
aerobic
respiration,
death
cell.
review,
we
discuss
latest
findings
on
mechanisms
molecular
controlling
mtDNA
release.
We
also
explored
connection
between
misplacement
activation.
Additionally,
propose
potential
therapeutic
targets
for
treatment.
Язык: Английский