Preferential transport of synaptic vesicles across neuronal branches is regulated by the levels of the anterograde motor UNC-104/KIF1A in vivo
Genetics,
Год журнала:
2024,
Номер
227(1)
Опубликована: Фев. 14, 2024
Abstract
Asymmetric
transport
of
cargo
across
axonal
branches
is
a
field
active
research.
Mechanisms
contributing
to
preferential
along
specific
in
vivo
wild
type
neurons
are
poorly
understood.
We
find
that
anterograde
synaptic
vesicles
preferentially
enter
the
branch
or
pause
at
point
Caenorhabditis
elegans
Posterior
Lateral
Mechanosensory
neurons.
The
vesicle
kinesin
motor
UNC-104/KIF1A
regulates
this
behavior
point.
Reduced
levels
functional
UNC-104
cause
predominantly
and
lose
their
preference
for
turning
into
branch.
SAM-4/Myrlysin,
which
aids
recruitment/activation
on
vesicles,
similar
UNC-104.
Increasing
increases
go
straight
toward
asynaptic
end.
This
suggests
neuron
optimizes
surface
maximize
fraction
entering
minimize
going
Язык: Английский
BORC segregates synaptic vesicle and lysosomal proteins through motors UNC-104/KIF1A and UNC-116/KIF5
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 1, 2025
Abstract
While
synaptic
vesicle
proteins
(SVPs)
and
lysosomal
can
be
present
together
in
axons,
the
origin
of
these
compartments
is
unclear.
These
SV-lysosomes
are
however
thought
to
segregate
further
SVPs
proteins.
In
this
study,
we
identify
genes
characterize
a
genetic
pathway
involved
segregation
neuronal
cell
body.
We
novel
role
for
BORC
(BLOC-1-related
complex)
segregating
subunit
SAM-4/Myrlysin
acts
through
ARL-8
Kinesin
motor
UNC-116/KIF5
UNC-104/KIF1A
Additionally,
also
show
that
LRK-1/LRRK2
APB-3/AP-3
(β3),
pre-SV
biogenesis,
regulate
LRK-1
recruits
SAM-4
turn
governs
localisation
APB-3
suggesting
hierarchical
LRK-1-SAM-4-APB-3
observe
size
protein-containing
(LPCCs)
smaller
LRK-1.
This
regulation
depends
on
UNC-116.
Together,
recruited
by
via
motors
along
with
AP-3
mediates
Язык: Английский
Roles of LRRK2 and its orthologs in protecting against neurodegeneration and neurodevelopmental defects
Frontiers in Cell and Developmental Biology,
Год журнала:
2025,
Номер
13
Опубликована: Апрель 30, 2025
In
humans,
variants
in
the
LRRK2
gene
are
most
prevalent
risk
factors
for
Parkinson's
disease
(PD).
Whereas
studies
model
organisms
have
long
indicated
that
orthologs
of
wild-type
LRRK
proteins
protect
against
neurodegeneration,
newer
findings
indicate
they
also
neurodevelopmental
defects.
This
normal
role
can
be
disrupted
by
either
gain-of-function
(GOF)
or
loss-of-function
(LOF)
mutations,
leading
to
neurodegeneration
and
Here,
we
review
roles
their
these
processes,
with
a
focus
on
autophagy
as
common
factor
may
mediate
both
roles.
We
highlight
potential
experiments
vertebrate
invertebrate
systems
synergistically
inform
our
understanding
protecting
neurological
disorders.
Язык: Английский
Biogenesis and reformation of synaptic vesicles
The Journal of Physiology,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 5, 2024
Abstract
Communication
within
the
nervous
system
relies
on
calcium‐triggered
release
of
neurotransmitter
molecules
by
exocytosis
synaptic
vesicles
(SVs)
at
defined
active
zone
sites.
While
decades
research
have
provided
detailed
insight
into
molecular
machinery
for
SV
fusion,
much
less
is
known
about
mechanisms
that
form
functional
SVs
during
development
synapses
and
control
local
reformation
following
in
mature
system.
Here
we
review
current
state
knowledge
field,
focusing
pathways
implicated
formation
axonal
transport
precursor
organelles
involved
nerve
terminals
neurons.
We
discuss
open
questions
outline
perspectives
future
research.
image
Язык: Английский