α-catenin phosphorylation is elevated during mitosis to resist apical rounding and epithelial barrier leak
Biology Open,
Год журнала:
2025,
Номер
14(1)
Опубликована: Янв. 8, 2025
ABSTRACT
Epithelial
cell
cohesion
and
barrier
function
critically
depend
on
α-catenin,
an
actin-binding
protein
essential
constituent
of
cadherin-catenin-based
adherens
junctions.
α-catenin
undergoes
actomyosin
force-dependent
unfolding
both
middle
domains
to
strongly
engage
actin
filaments
its
various
effectors;
this
mechanosensitivity
is
critical
for
junction
function.
We
previously
showed
that
highly
phosphorylated
in
unstructured
region
links
the
mechanosensitive
(known
as
P-linker
region),
but
cellular
processes
promote
phosphorylation
have
remained
elusive.
Here,
we
leverage
a
published
phospho-proteomic
data
set
show
maximally
during
mitosis.
By
reconstituting
CRISPR
knockout
MDCK
cells
with
wild-type,
phospho-mutant
phospho-mimic
forms
full
restrains
mitotic
rounding
apical
direction,
strengthening
interactions
between
dividing
non-dividing
neighbors
limit
epithelial
leak.
As
major
scaffold
components
junctions,
tight
junctions
desmosomes
are
also
differentially
mitosis,
reason
division
may
be
tractable
system
understand
how
complexes
coordinately
regulated
sustain
under
tension-generating
morphogenetic
processes.
Язык: Английский
Nanoparticle Interactions with the Blood Brain Barrier: Insights from Drosophila and Implications for Human Astrocyte Targeted Therapies
Neurochemical Research,
Год журнала:
2025,
Номер
50(1)
Опубликована: Янв. 20, 2025
Язык: Английский
Vertex remodeling during epithelial morphogenesis
Current Opinion in Cell Biology,
Год журнала:
2024,
Номер
91, С. 102427 - 102427
Опубликована: Сен. 26, 2024
Epithelial
cells
adhere
to
each
other
via
intercellular
junctions
that
can
be
classified
into
bicellular
and
tricellular
contacts
(vertices).
morphogenesis
involves
cell
rearrangement
requires
remodeling
of
vertices.
Although
our
understanding
how
junction
mechanics
drive
epithelial
has
advanced,
the
mechanisms
underlying
vertex
during
this
process
have
only
received
attention
recently.
In
review,
we
outline
recent
progress
in
reorganize
adhesion
cytoskeleton
trigger
displacement
resolution
We
will
also
discuss
achieve
optimal
balance
between
structural
flexibility
stability
their
Finally,
introduce
new
modeling
frameworks
designed
analyze
at
Integration
live
imaging
techniques
is
providing
insights
active
roles
vertices
morphogenesis.
Язык: Английский
Rift Valley fever virus is able to cross the human blood–brain barrier in vitro by direct infection with no deleterious effects
Journal of Virology,
Год журнала:
2024,
Номер
98(10)
Опубликована: Сен. 30, 2024
ABSTRACT
Rift
Valley
fever
(RVF)
is
a
zoonotic
arboviral
disease
that
causes
recurrent
epidemics
in
Africa
may
trigger
fatal
neurological
disorders.
However,
the
mechanisms
of
neuroinvasion
by
which
RVF
virus
(RVFV)
reaches
human
central
nervous
system
(CNS)
remain
poorly
characterized.
In
particular,
it
not
clear
how
RVFV
able
to
cross
blood–brain
barrier
(hBBB),
neurovascular
endothelium
protects
brain
regulating
and
blood
exchanges.
To
explore
these
mechanisms,
we
used
an
vitro
hBBB
model
mimic
vivo
selectiveness
apicobasal
polarity.
Our
results
highlight
ability
direct
infection
non-structural
protein
S
(NSs)-independent
but
strain-dependent
manner,
leading
astrocyte
pericyte
infections.
Interestingly,
did
induce
disruption
was
associated
with
progressive
elimination
infected
cells
no
impairment
tight
junction
scaffold
function.
work
also
shows
NSs,
well
described
virulence
factor,
limited
establishment
hBBB-induced
innate
immune
response
subsequent
lymphocyte
recruitment.
These
provide
confirmation
reach
CNS
without
altering
its
function,
new
directions
neurovirulence
mechanisms.
IMPORTANCE
The
capable
infecting
humans
inducing
severe
Neuropathogenesis
invasion
are
still
unknown,
only
historical
studies
autopsy
data
from
cases
1980s
exploration
rodent
models.
One
gaps
understanding
pathogenesis
(BBB)
order
CNS.
For
first
time,
show
directly
infect
BBB
release
viral
particles
into
CNS,
well-characterized
mechanism
pathogens.
Furthermore,
demonstrate
variability
this
mechanism,
identifying
possible
properties
could
be
explored
prevent
disorders
during
outbreaks.
Язык: Английский
Anillin tunes contractility and regulates barrier function during Rho flare-mediated tight junction remodeling
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 21, 2024
Abstract
To
preserve
barrier
function,
cell-cell
junctions
must
dynamically
remodel
during
cell
shape
changes.
We
have
previously
described
a
rapid
tight
junction
repair
pathway
characterized
by
local,
transient
activation
of
RhoA,
termed
‘Rho
flares,’
which
leaks
in
via
promoting
local
actomyosin-mediated
remodeling.
In
this
pathway,
elongation
is
mechanical
trigger
that
initiates
RhoA
through
an
influx
intracellular
calcium
and
recruitment
p115RhoGEF.
However,
mechanisms
tune
the
level
Myosin
II
contractility
process
remain
uncharacterized.
Here,
we
show
scaffolding
protein
Anillin
localizes
to
Rho
flares
regulates
activity
actomyosin
contraction
at
flares.
Knocking
down
results
with
increased
intensity
but
shorter
duration.
These
changes
active
dynamics
weaken
downstream
F-actin
accumulation
site
flares,
resulting
decreased
contraction.
Consequently,
breaks
are
not
reinforced
following
Anillin-driven
regulation
necessary
for
successfully
repairing
protecting
from
repeated
damage.
Together,
these
uncover
novel
regulatory
role
function
maintenance.
Significance
Statement
Barrier
critical
epithelial
tissues.
Epithelial
cells
maintain
junctions,
be
remodeled
allow
cell-
tissue-scale
How
maintained
as
change
remains
unclear.
The
required
generating
effective
reinforce
damaged
junctions;
lack
reinforcement
leads
leaks.
findings
highlight
remodeling
suggest
Anillin’s
ability
duration
affects
contractile
output.
Язык: Английский