α-Synuclein interacts directly with AP2 and regulates its binding to synaptic membranes
Journal of Biological Chemistry,
Год журнала:
2025,
Номер
unknown, С. 108502 - 108502
Опубликована: Апрель 1, 2025
Язык: Английский
Live-cell quantification reveals viscoelastic regulation of synapsin condensates by α-synuclein
Science Advances,
Год журнала:
2025,
Номер
11(16)
Опубликована: Апрель 18, 2025
Synapsin
and
α-synuclein
represent
a
growing
list
of
condensate-forming
proteins
where
the
material
states
condensates
are
directly
linked
to
cellular
functions
(e.g.,
neurotransmission)
pathology
neurodegeneration).
However,
quantifying
condensate
properties
in
living
systems
has
been
substantial
challenge.
Here,
we
develop
micropipette
aspiration
whole-cell
patch-clamp
(MAPAC),
platform
that
allows
direct
quantification
live
cells.
We
find
10,000-fold
variations
viscoelasticity
synapsin
condensates,
regulated
by
partitioning
α-synuclein,
marker
for
synucleinopathies.
Through
vitro
reconstitutions,
identify
multiple
molecular
factors
distinctly
regulate
viscosity,
interfacial
tension,
maturation
confirming
roles
α-synuclein.
Overall,
our
study
provides
unprecedented
quantitative
insights
into
neuronal
reveals
crucial
role
regulating
viscoelasticity.
Furthermore,
envision
MAPAC
applicable
broad
range
vivo.
Язык: Английский
Loss of intracellular ATP affects axoplasmic viscosity and pathological protein aggregation in mammalian neurons
Science Advances,
Год журнала:
2025,
Номер
11(17)
Опубликована: Апрель 23, 2025
Neurodegenerative
diseases
display
synaptic
deficits,
mitochondrial
defects,
and
protein
aggregation.
We
show
that
intracellular
adenosine
triphosphate
(ATP)
regulates
axoplasmic
viscosity
aggregation
in
mammalian
neurons.
Decreased
ATP
upon
inhibition
leads
to
axoterminal
cytosol,
vesicles,
active
zone
component
condensation,
modulating
the
functional
organization
of
mouse
glutamatergic
synapses.
Proteins
involved
pathogenesis
Parkinson’s
disease
(PD),
Alzheimer’s
(AD),
amyotrophic
lateral
sclerosis
(ALS)
condensed
underwent
ATP-dependent
liquid
phase
separation
vitro.
Human
inducible
pluripotent
stem
cell–derived
neurons
from
patients
with
PD
ALS
displayed
reduced
fluidity
decreased
ATP.
Last,
nicotinamide
mononucleotide
treatment
successfully
rescued
levels
TAR
DNA-binding
43
(TDP-43)
human
motor
derived
a
patient
ALS.
Thus,
our
data
suggest
hydrotropic
activity
contributes
regulation
neuronal
homeostasis
under
both
physiological
pathological
conditions.
Язык: Английский
α-Synuclein condensation in synaptic vesicle function and synucleinopathies
Trends in Cell Biology,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 1, 2025
Язык: Английский
Direct quantification of condensate material properties in live cells reveals the regulation of synapsin condensates viscoelasticity by alpha-synuclein
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Июль 29, 2024
Synapsin
and
α-synuclein
represent
a
growing
list
of
condensate-forming
proteins
where
the
material
states
condensates
are
directly
linked
to
cellular
functions
(e.g.,
neurotransmission)
pathology
neurodegeneration).
However,
quantifying
condensate
properties
in
living
systems
has
been
significant
challenge.
To
address
this,
we
develop
MAPAC
(micropipette
aspiration
whole-cell
patch
clamp),
platform
that
allows
direct
quantification
live
cells.
We
find
10,000-fold
variations
viscoelasticity
synapsin
condensates,
regulated
by
partitioning
α-synuclein,
marker
for
synucleinopathies.
Through
vitro
reconstitutions,
identify
4
molecular
factors
distinctly
regulate
viscosity
interfacial
tension
verifying
effects
α-synuclein.
Overall,
our
study
provides
unprecedented
quantitative
insights
into
neuronal
reveals
crucial
role
regulating
viscoelasticity.
Furthermore,
envision
applicable
broad
range
vivo.
Язык: Английский
Liquid–liquid phase separation in presynaptic nerve terminals
Trends in Biochemical Sciences,
Год журнала:
2024,
Номер
49(10), С. 888 - 900
Опубликована: Авг. 27, 2024
Язык: Английский
A role for synapsin tetramerization in synaptic vesicle clustering
The Journal of Physiology,
Год журнала:
2024,
Номер
unknown
Опубликована: Июль 9, 2024
Abstract
Although
synapsins
have
long
been
proposed
to
be
key
regulators
of
synaptic
vesicle
(SV)
clustering,
their
mechanism
action
has
remained
mysterious
and
somewhat
controversial.
Here,
we
review
associations
with
each
other
SVs.
We
highlight
the
recent
hypothesis
that
synapsin
tetramerization
is
a
for
SV
clustering.
This
hypothesis,
which
aligns
numerous
experimental
results,
suggests
larger
size
tetramers,
in
comparison
dimers,
allows
tetramers
form
optimal
bridges
between
SVs
overcome
repulsive
force
associated
negatively
charged
membrane
allow
reserve
pool
within
presynaptic
terminals.
image
Язык: Английский