Current Biology,
Год журнала:
2023,
Номер
33(5), С. 858 - 874.e7
Опубликована: Фев. 13, 2023
Cell
proliferation
is
central
to
epithelial
tissue
development,
repair,
and
homeostasis.
During
cell
division,
small
RhoGTPases
control
both
actomyosin
dynamics
cell-cell
junction
remodeling
faithfully
segregate
the
genome
while
maintaining
polarity
integrity.
To
decipher
mechanisms
of
RhoGTPase
spatiotemporal
regulation
during
we
generated
a
transgenic
fluorescently
tagged
library
for
48
Drosophila
Rho
guanine
exchange
factors
(RhoGEFs)
GTPase-activating
proteins
(GAPs),
systematically
characterized
their
endogenous
distributions
by
time-lapse
microscopy.
Therefore,
unveiled
candidate
regulators
interplay
between
junctional
division.
Building
on
these
findings,
established
that
conserved
RhoGEF
Cysts
RhoGEF4
play
sequential
distinct
roles
couple
cytokinesis
with
de
novo
formation.
ring
contraction,
via
Rho1
participates
in
neighbor
mechanosensing
response,
promoting
daughter-daughter
membrane
juxtaposition
preparation
Subsequently
upon
midbody
formation,
Rac
acts
dividing
ensure
withdrawal
neighboring
membranes,
thus
controlling
length
arrangements
cytokinesis.
Altogether,
our
findings
delineate
how
are
locally
temporally
activated
cytokinesis,
highlighting
RhoGEF/GAP
as
key
resource
understand
broad
range
biological
processes
regulated
RhoGTPases.
Biochimica et Biophysica Acta (BBA) - Biomembranes,
Год журнала:
2020,
Номер
1862(9), С. 183316 - 183316
Опубликована: Апрель 28, 2020
Epithelial
and
endothelial
monolayers
are
multicellular
sheets
that
form
barriers
between
the
'outside'
'inside'
of
tissues.
Cell-cell
junctions,
made
by
adherens
tight
junctions
desmosomes,
hold
together
these
monolayers.
They
intercellular
contacts
binding
their
receptor
counterparts
on
neighboring
cells
anchoring
structures
intracellularly
to
cytoskeleton.
During
tissue
development,
maintenance
pathogenesis,
encounter
a
range
mechanical
forces
from
themselves
external
systemic
forces,
such
as
blood
pressure
or
stiffness.
The
molecular
landscape
cell-cell
is
diverse,
containing
transmembrane
proteins
bonds
variety
cytoplasmic
remodel
junctional
connection
Many
junction-associated
participate
in
mechanotransduction
cascades
confer
cues
into
cellular
responses
allow
maintain
structural
integrity.
We
will
discuss
force-dependent
events
role
contact
organization
remodeling.
Current Biology,
Год журнала:
2019,
Номер
29(20), С. 3370 - 3385.e7
Опубликована: Сен. 12, 2019
Small
RhoGTPases
direct
cell
shape
changes
and
movements
during
tissue
morphogenesis.
Their
activities
are
tightly
regulated
in
space
time
to
specify
the
desired
pattern
of
actomyosin
contractility
that
supports
This
is
expected
stem
from
polarized
surface
stimuli
signaling
processing
inside
cells.
We
examined
this
general
problem
context
intercalation
drives
extension
Drosophila
ectoderm.
In
ectoderm,
G
protein-coupled
receptors
(GPCRs)
their
downstream
heterotrimeric
proteins
(Gα
Gβγ)
activate
Rho1
both
medial-apically,
where
it
exhibits
pulsed
dynamics,
at
junctions,
its
activity
planar
polarized.
However,
mechanisms
responsible
for
polarizing
unclear.
report
distinct
guanine
exchange
factors
(GEFs)
these
two
cellular
compartments.
RhoGEF2
acts
uniquely
medial-apical
but
recruited
medial-apically
junctions
by
Gα12/13-GTP,
also
called
Concertina
(Cta)
Drosophila.
On
other
hand,
Dp114RhoGEF
(Dp114),
a
newly
characterized
RhoGEF,
required
extending
activates
specifically
junctions.
Its
localization
restricted
adherens
under
Gβ13F/Gγ1
control.
Furthermore,
junctional
exerts
quantitative
control
over
polarization
Rho1.
Finally,
we
found
absent
mesoderm,
arguing
tissue-specific
activity.
These
results
clarify
different
compartments
reveal
GEFs
sensitive
tuning
parameters
remodeling
epithelia.
Cell Reports,
Год журнала:
2020,
Номер
32(3), С. 107924 - 107924
Опубликована: Июль 1, 2020
Tight-junction-regulated
actomyosin
activity
determines
epithelial
and
endothelial
tension
on
adherens
junctions
drives
morphogenetic
processes;
however,
whether
or
not
tight
themselves
are
under
tensile
stress
is
clear.
Here,
we
use
a
sensor
based
ZO-1,
scaffolding
protein
that
links
the
junctional
membrane
to
cytoskeleton,
determine
if
carry
mechanical
load.
Our
data
indicate
ZO-1
forces
acting
regulated
by
extracellular
matrix
(ECM)
stiffness
adhesion
molecule
JAM-A.
JAM-A
depletion
stimulates
recruitment
of
p114RhoGEF/ARHGEF18,
traction
at
focal
adhesions.
p114RhoGEF
required
for
activation
junction
integrity
stiff
but
soft
ECM.
Thus,
bears
load,
assembly
interplay
between
physical
properties
ECM
adhesion-regulated
signaling
junctions.
The Journal of Cell Biology,
Год журнала:
2022,
Номер
221(4)
Опубликована: Март 7, 2022
Epithelial
cell–cell
junctions
remodel
in
response
to
mechanical
stimuli
maintain
barrier
function.
Previously,
we
found
that
local
leaks
tight
(TJs)
are
rapidly
repaired
by
local,
transient
RhoA
activation,
termed
“Rho
flares,”
but
how
Rho
flares
regulated
is
unknown.
Here,
discovered
intracellular
calcium
flashes
and
junction
elongation
early
events
the
flare
pathway.
Both
laser-induced
naturally
occurring
TJ
breaks
lead
at
site
of
leaks.
Additionally,
induced
optogenetics
increases
frequency,
suggesting
mechanically
triggered.
Depletion
or
inhibition
mechanosensitive
channels
(MSCs)
reduces
amplitude
diminishes
sustained
activation
flares.
MSC-dependent
influx
necessary
global
function
regulating
reinforcement
proteins
via
contraction.
In
all,
uncovered
a
novel
role
for
remodeling,
allowing
epithelial
cells
repair
stimuli.
