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.
Chemical Society Reviews,
Год журнала:
2024,
Номер
53(10), С. 4976 - 5013
Опубликована: Янв. 1, 2024
Protein
misfolding
and
amyloid
aggregation,
linked
to
neurodegenerative
diseases,
can
result
from
liquid–liquid
phase
separation
(LLPS)
a
subsequent
liquid-to-solid
transition.
This
represents
LLPS
as
generic
mechanism
in
nucleation.
Physiological Reviews,
Год журнала:
2024,
Номер
105(1), С. 441 - 491
Опубликована: Авг. 22, 2024
In
the
past
decade,
evidence
for
numerous
roles
of
copper
(Cu)
in
mammalian
physiology
has
grown
exponentially.
The
discoveries
Cu
involvement
cell
signaling,
autophagy,
motility,
differentiation,
and
regulated
death
(cuproptosis)
have
markedly
extended
list
already
known
functions
Cu,
such
as
a
cofactor
essential
metabolic
enzymes,
protein
structural
component,
regulator
trafficking.
Novel
unexpected
transporting
proteins
enzymes
been
identified,
new
disorders
homeostasis
described.
Significant
progress
made
mechanistic
studies
two
classic
metabolism,
Menkes
disease
Wilson’s
disease,
which
paved
way
novel
approaches
to
their
treatment.
discovery
cuproptosis
role
metastatic
growth
increased
interest
targeting
homeostatic
pathways
treat
cancer.
this
review,
we
summarize
established
concepts
field
discuss
how
decade
expand
modify
these
concepts.
brain
metabolism
functional
speciation
recently
discovered
attracted
significant
attention
are
highlighted
review.
Journal of Biological Chemistry,
Год журнала:
2024,
Номер
300(6), С. 107310 - 107310
Опубликована: Апрель 22, 2024
Liquid-liquid
phase
separation
(LLPS)
of
the
mammalian
prion
protein
is
mainly
driven
by
its
intrinsically
disordered
N-terminal
domain
(N-PrP).
However,
specific
intermolecular
interactions
that
promote
LLPS
remain
largely
unknown.
Here,
we
used
extensive
mutagenesis
and
comparative
analyses
evolutionarily
distant
PrP
species
to
gain
insight
into
relationship
between
sequence
behavior.
mouse
dependent
on
two
polybasic
motifs
in
N-PrP
are
conserved
all
tetrapods.
A
unique
feature
octarepeat
with
four
histidines
mediate
binding
copper
ions.
We
now
show
critical
for
promoting
preventing
formation
aggregates.
Amphibian
N-PrP,
which
contains
but
lacks
a
repeat
histidines,
does
not
undergo
forms
nondynamic
assemblies
indicative
Insertion
restored
amphibian
supporting
essential
role
regulating
transition
PrP.
This
activity
was
neither
highly
nor
binding.
Instead,
regularly
spaced
tryptophan
residues
were
LLPS,
presumably
via
cation-π
motifs.
Our
study
reveals
novel
controlling
indicates
ability
has
evolved
independently
histidines.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Март 11, 2025
Abstract
Microbes
must
rapidly
adapt
to
environmental
stresses,
including
toxic
heavy
metals
like
copper,
by
sensing
and
mitigating
their
harmful
effects.
Here,
we
demonstrate
that
the
phase
separation
properties
of
bacterial
ribonucleoprotein
bodies
(BR-bodies)
enhance
Caulobacter
crescentus
fitness
under
copper
stress.
To
uncover
underlying
mechanism,
identified
two
key
interactions
between
central
scaffold
BR-bodies,
RNase
E.
First,
biochemical
assays
fluorescence
microscopy
experiments
show
reductive
chelation
Cu²⁺
leads
cysteine
oxidation,
driving
transition
BR-bodies
into
more
solid-like
condensates.
Second,
tryptophan
EPR
reveal
E
binds
at
histidine
sites,
creating
a
protective
microenvironment
prevents
mismetallation
preserves
PNPase
activity.
More
broadly,
this
example
highlights
how
metal-condensate
can
regulate
condensate
material
establish
specialized
chemical
environments
safeguard
enzyme
function.
Life
is
inherently
heterogeneous,
and
visualizing
this
heterogeneity
in
the
spatial
distribution
of
biometals
offers
valuable
insights
into
various
biological
processes.
While
biometal
mapping
provides
superior
resolution
compared
to
other
bioanalytical
techniques,
it
alone
cannot
fully
explain
functional
roles
health
disease.
In
study,
we
introduced
a
novel
method
using
specially
designed
sample
grids
facilitate
beam-,
X-ray-,
ion-beam-based
imaging
on
same
tissue
section.
This
innovative
approach
aligns
integrates
nanoscale-resolved
iron
profiles
across
spatial,
chemical,
isotopic
dimensions.
By
combining
these
analyses,
achieved
unprecedented
detail,
revealing
complex
regulatory
framework
homeostasis
liver
tissues
following
overload.
These
findings
demonstrate
that
enhancing
both
information
content
analysis
can
overcome
current
limitations,
providing
new
molecular
mechanisms
underlying
functions.
