Journal of Cell Science,
Год журнала:
2024,
Номер
137(24)
Опубликована: Дек. 13, 2024
ABSTRACT
Protein
liquid–liquid
phase
separation
(LLPS)
is
driven
by
intrinsically
disordered
regions
and
multivalent
binding
domains,
both
of
which
are
common
features
diverse
microtubule
(MT)
regulators.
Many
in
vitro
studies
have
dissected
the
mechanisms
MT-binding
proteins
(MBPs)
regulate
MT
nucleation,
stabilization
dynamics,
investigated
whether
LLPS
plays
a
role
these
processes.
However,
more
recent
vivo
focused
on
how
MBP
affects
biological
functions
throughout
neuronal
development.
Dysregulation
can
lead
to
formation
aggregates
–
an
underlying
feature
many
neurodegenerative
diseases
such
as
tau
neurofibrillary
tangles
present
Alzheimer's
disease.
In
this
Review,
we
highlight
progress
towards
understanding
regulation
dynamics
through
lens
MBPs
associated
cytoskeletal
regulators,
from
studies.
We
also
discuss
regulates
development
maintains
homeostasis
mature
neurons.
Abstract
Eukaryotic
cells
have
developed
intricate
mechanisms
for
biomolecule
transport,
particularly
in
stressful
conditions.
This
interdisciplinary
study
delves
into
unconventional
protein
secretion
(UPS)
pathways
activated
during
starvation,
facilitating
the
export
of
proteins
bypassing
most
components
classical
secretory
machinery.
Specifically,
we
focus
on
underexplored
GRASP's
role
UPS,
biogenesis
and
cargo
recruitment
vesicular‐like
compartment
UPS.
Our
results
show
that
liquid–liquid
phase
separation
(LLPS)
plays
a
key
coacervation
Grh1,
GRASP
yeast
homologue,
under
starvation‐like
association
seems
precursor
to
Compartment
Unconventional
Protein
Secretion
(CUPS)
biogenesis.
Grh1's
self‐association
is
regulated
by
electrostatic,
hydrophobic,
hydrogen‐bonding
interactions.
Importantly,
our
demonstrates
phase‐separated
states
Grh1
can
recruit
UPS
situations.
Additionally,
explore
how
coacervate
liquid‐to‐solid
transition
could
impact
cells'
ability
return
normal
post‐stress
states.
findings
offer
insights
intracellular
dynamics
cell
adaptive
responses
stress.
In
biological
systems,
nanoparticles
interact
with
biomolecules,
which
may
undergo
protein
corona
formation
that
can
result
in
noncontrolled
aggregation.
Therefore,
comprehending
the
behavior
and
evolution
of
presence
fluids
is
paramount
nanomedicine.
However,
traditional
lab-based
colloid
methods
characterize
diluted
suspensions
low-complexity
media,
hinders
in-depth
studies
complex
environments.
Here,
we
apply
X-ray
photon
correlation
spectroscopy
(XPCS)
to
investigate
silica
(SiO
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Окт. 25, 2024
Physical
properties
of
biomolecular
condensates
formed
via
phase
separation
proteins
and
nucleic
acids
are
associated
with
cell
physiology
disease.
Condensate
can
be
regulated
by
several
cellular
factors
including
post-translational
modifications.
Here,
we
introduce
an
application
intermolecular
energy
migration
homo-FRET
(Förster
resonance
transfer),
a
nanometric
proximity
ruler,
to
study
the
modulation
in
short-
long-range
protein-protein
interactions
leading
changes
physical
fluorescently-tagged
FUS
(Fused
Sarcoma)
that
is
formation
cytoplasmic
nuclear
membraneless
organelles.
We
show
homoFRET
captures
modulations
condensate
RNA,
ATP,
arginine
methylation.
also
extend
methodology
in-situ
stress
granules
mammalian
cells.
Our
studies
highlight
broad
applicability
as
potent
generic
tool
for
studying
intracellular
transitions
involved
function
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Фев. 12, 2024
Abstract
Biomolecular
condensation
via
phase
separation
of
proteins
and
nucleic
acids
has
emerged
as
a
crucial
mechanism
underlying
the
spatiotemporal
organization
cellular
components
into
functional
membraneless
organelles.
However,
aberrant
maturation
these
dynamic,
liquid-like
assemblies
irreversible
gel-like
or
solid-like
aggregates
is
associated
with
wide
range
fatal
neurodegenerative
diseases.
New
tools
are
essential
to
dissect
changes
in
internal
material
properties
biomolecular
condensates
that
often
modulated
by
factors
involving
sequence
composition,
truncations,
mutations,
post-translational
modifications,
stoichiometry
other
biomolecules.
Here,
we
employ
homo-Förster
Resonance
Energy
Transfer
(homoFRET)
proximity
ruler
study
intermolecular
energy
migration
illuminates
molecular
packing
nanometric
length-scale
within
condensates.
We
used
homoFRET
efficiency,
measured
loss
fluorescence
anisotropy
due
rapid
depolarization,
readout
giving
rise
Using
single-droplet
imaging,
recorded
spatially-resolved
efficiencies
formed
fluorescent
protein-tagged
Fused
Sarcoma
(FUS).
By
performing
picosecond
time-resolved
measurements,
were
able
discern
various
events
dense
network
polypeptide
chains
FUS
Our
studies
also
captured
modulation
RNA,
ATP,
modification.
Additionally,
utilized
mammalian
cell
lines
stably
expressing
nuclear
oxidative
stress-induced
stress
granule
formation
cytoplasm.
demonstrate
methodology
offers
potent
tool
for
studying
intracellular
transitions
physiology
disease.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 8, 2024
Abstract
Biomolecular
condensates
formed
via
phase
separation
of
proteins
and
nucleic
acids
are
crucial
for
the
spatiotemporal
regulation
a
diverse
array
essential
cellular
functions
maintenance
homeostasis.
However,
aberrant
liquid-to-solid
transitions
such
associated
with
several
fatal
human
diseases.
Such
dynamic
membraneless
compartments
can
contain
range
molecular
chaperones
that
regulate
behavior
involved
in
formation
these
biological
condensates.
Here,
we
show
heat
shock
protein
40
(Hsp40),
Ydj1,
exhibits
holdase
activity
by
potentiating
disease-associated
stop
codon
mutant
prion
(Y145Stop)
either
recruitment
into
Y145Stop
or
Y145Stop-Ydj1
two-component
heterotypic
prevents
conformational
conversion
amyloid
fibrils.
Utilizing
site-directed
mutagenesis,
multicolor
fluorescence
imaging,
single-droplet
steady-state
picosecond
time-resolved
anisotropy,
recovery
after
photobleaching,
correlation
spectroscopy,
delineate
complex
network
interactions
govern
Ydj1.
We
also
properties
further
be
tuned
RNA
promotes
multicomponent
multiphasic
protein-RNA
Our
vibrational
Raman
spectroscopy
results
conjunction
atomic
force
microscopy
imaging
reveal
Ydj1
effectively
redirects
self-assembly
towards
dynamically-arrested
non-amyloidogenic
pathway,
preventing
typical
findings
underscore
importance
chaperone-mediated
regulating
wide
deadly
neurodegenerative
Journal of Cell Science,
Год журнала:
2024,
Номер
137(24)
Опубликована: Дек. 13, 2024
ABSTRACT
Protein
liquid–liquid
phase
separation
(LLPS)
is
driven
by
intrinsically
disordered
regions
and
multivalent
binding
domains,
both
of
which
are
common
features
diverse
microtubule
(MT)
regulators.
Many
in
vitro
studies
have
dissected
the
mechanisms
MT-binding
proteins
(MBPs)
regulate
MT
nucleation,
stabilization
dynamics,
investigated
whether
LLPS
plays
a
role
these
processes.
However,
more
recent
vivo
focused
on
how
MBP
affects
biological
functions
throughout
neuronal
development.
Dysregulation
can
lead
to
formation
aggregates
–
an
underlying
feature
many
neurodegenerative
diseases
such
as
tau
neurofibrillary
tangles
present
Alzheimer's
disease.
In
this
Review,
we
highlight
progress
towards
understanding
regulation
dynamics
through
lens
MBPs
associated
cytoskeletal
regulators,
from
studies.
We
also
discuss
regulates
development
maintains
homeostasis
mature
neurons.
