Journal of Cell Science,
Год журнала:
2024,
Номер
137(9)
Опубликована: Май 1, 2024
ABSTRACT
Tight
junctions
(TJs)
are
specialized
regions
of
contact
between
cells
epithelial
and
endothelial
tissues
that
form
selective
semipermeable
paracellular
barriers
establish
maintain
body
compartments
with
different
fluid
compositions.
As
such,
the
formation
TJs
represents
a
critical
step
in
metazoan
evolution,
allowing
multicompartmental
organisms
true,
barrier-forming
epithelia
endothelia.
In
six
decades
have
passed
since
first
observations
by
transmission
electron
microscopy,
much
progress
has
been
made
understanding
structure,
function,
molecular
composition
regulation
TJs.
The
goal
this
Perspective
is
to
highlight
key
concepts
emerged
through
research
future
challenges
lie
ahead
for
field.
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.
The
network
of
proteins
at
the
interface
between
cell-cell
adherens
junctions
and
actomyosin
cytoskeleton
provides
robust
yet
dynamic
connections
that
facilitate
cell
shape
change
motility.
While
this
was
initially
thought
to
be
a
simple
linear
connection
via
classic
cadherins
their
associated
catenins,
we
now
have
come
appreciate
many
more
are
involved,
providing
robustness
mechanosensitivity.
Defining
full
set
in
remains
key
objective
our
field.
Proximity
proteomics
means
define
these
networks.
Mammalian
Afadin
its
Drosophila
homolog
Canoe
parts
protein
network,
facilitating
diverse
changes
during
gastrulation
other
events
embryonic
morphogenesis.
Here
report
results
several
proximity
screens,
defining
neighborhood
both
N-
C-termini
mammalian
premier
epithelial
model,
MDCK
cells.
We
compare
with
previous
screens
done
types,
efforts
junctional
proteins.
These
reveal
value
multiple
neighbors
offer
interesting
insights
into
overlap
composition
different
junctions.
Journal of Agricultural and Food Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 12, 2025
The
food
safety
risks
posed
by
exposure
to
polystyrene
microplastics
(PS-MPs)
and
bisphenol
A
(BPA)
have
become
an
issue
worldwide.
However,
the
toxic
effects
of
PS-MPs
BPA
coexposure
on
mammalian
liver
remain
elusive.
In
this
study,
we
found
that
synergistic
AML12
cells
mouse
liver.
Histopathological
staining
revealed
excessive
accumulation
extracellular
matrix
in
Co-exposure
downregulated
Bmal1
E-cad
both
vitro
vivo.
Additionally,
Bmal1–/–
liver-specific
mice
exhibited
significantly
reduced
levels,
with
no
significant
reduction
under
coexposure.
Notably,
overexpression
BMAL1
CLOCK
enhanced
luciferase
activity
driven
gene
intron
region
(containing
E-box
cis-element).
These
results
demonstrated
contributed
development
fibrosis
inhibiting
BMAL1/E-cad
signaling
pathway.
European Journal of Cell Biology,
Год журнала:
2024,
Номер
103(2), С. 151410 - 151410
Опубликована: Апрель 3, 2024
Epithelial
tissues
cover
the
surfaces
and
lumens
of
internal
organs
multicellular
animals
crucially
contribute
to
environment
homeostasis
by
delineating
distinct
compartments
within
body.
This
vital
role
is
known
as
epithelial
barrier
function.
cells
are
arranged
like
cobblestones
intricately
bind
together
form
an
sheet
that
upholds
this
Central
restriction
solute
fluid
diffusion
through
intercellular
spaces
occluding
junctions,
tight
junctions
in
vertebrates
septate
invertebrates.
As
part
tissues,
undergo
constant
renewal,
with
older
being
replaced
new
ones.
Simultaneously,
tissue
undergoes
relative
rearrangement,
elongating,
shifting
directionally
a
whole.
The
movement
or
shape
changes
necessitate
significant
deformation
reconnection
junctions.
Recent
advancements
have
shed
light
on
intricate
mechanisms
which
sustain
their
function
dynamic
environments.
review
aims
introduce
these
noteworthy
findings
discuss
some
questions
remain
unanswered.
The Journal of Cell Biology,
Год журнала:
2024,
Номер
223(5)
Опубликована: Апрель 2, 2024
Force
transmission
at
cell–cell
junctions
critically
regulates
embryogenesis,
tissue
homeostasis,
and
diseases
including
cancer.
The
cadherin–catenin
linkage
has
been
considered
the
keystone
of
junctional
force
transmission,
but
new
findings
challenge
this
paradigm,
arguing
instead
that
nectin–afadin
plays
more
important
role
in
mature
intestinal
epithelium.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Апрель 28, 2024
Summary
In
epithelial
cells,
cell-cell
adhesion
is
mediated
by
the
apical
junctional
complex
(AJC),
which
consists
of
tight
junctions
(TJs)
and
adherens
(AJs)
aligned
from
to
basal
axis.
However,
mechanism
AJC
formation
on
side
separation
these
within
AJCs
are
poorly
understood.
We
found
that
multivalent
interactions
afadin
with
molecules
cytoskeleton
lead
condensate
in
an
intrinsically
disordered
region
(IDR)-dependent
manner,
promotes
efficient
accumulation
linear
AJ
during
initial
junction
formation.
Furthermore,
we
ZO-1
were
able
induce
different
formations
cell
differentially
distributed
each
other.
These
properties
explain
how
it
strictly
localizes
AJs
cells
involved
regulating
segregation
TJ
AJC.
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.
Neural
lamination
is
a
common
feature
of
the
central
nervous
system
(CNS),
with
several
subcellular
structures,
such
as
adherens
junctions
(AJs),
playing
role
in
this
process.
The
retina
also
heavily
laminated,
but
it
remains
unclear
how
laminar
formation
impacts
retinal
cell
morphology,
synapse
integrity,
and
overall
function.
In
study,
we
demonstrate
that
loss
afadin,
key
component
AJs,
leads
to
significant
pathological
changes.
These
include
disruption
outer
notable
decrease
well
mislocalization
photoreceptors,
their
segments,
photoreceptor
synapses.
Interestingly,
despite
these
severe
impairments,
recorded
small
local
field
potentials,
including
a-
b-waves.
We
classified
ganglion
cells
into
ON,
ON-OFF,
OFF
types
based
on
firing
patterns
response
light
stimuli.
Additionally,
successfully
characterized
receptive
fields
certain
cells.
Overall,
findings
provide
first
evidence
circuit
function
can
be
partially
preserved
even
when
there
are
disruptions
Our
results
indicate
retinas
severely
altered
morphology
still
retain
some
capacity
process
Neural
lamination
is
a
common
feature
of
the
central
nervous
system
(CNS),
with
several
subcellular
structures,
such
as
adherens
junctions
(AJs),
playing
role
in
this
process.
The
retina
also
heavily
laminated,
but
it
remains
unclear
how
laminar
formation
impacts
retinal
cell
morphology,
synapse
integrity,
and
overall
function.
In
study,
we
demonstrate
that
loss
afadin,
key
component
AJs,
leads
to
significant
pathological
changes.
These
include
disruption
outer
notable
decrease
well
mislocalization
photoreceptors,
their
segments,
photoreceptor
synapses.
Interestingly,
despite
these
severe
impairments,
recorded
small
local
field
potentials,
including
a-
b-waves.
We
classified
ganglion
cells
into
ON,
ON-OFF,
OFF
types
based
on
firing
patterns
response
light
stimuli.
Additionally,
successfully
characterized
receptive
fields
certain
cells.
Overall,
findings
provide
first
evidence
circuit
function
can
be
partially
preserved
even
when
there
are
disruptions
Our
results
indicate
retinas
severely
altered
morphology
still
retain
some
capacity
process
