Cytoplasmic
dynein-mediated
intracellular
transport
needs
the
multi-component
dynactin
complex
for
cargo
binding
and
motor
activation.
However,
cellular
factors
involved
in
assembly
remain
unexplored.
Here
we
found
Aspergillus
nidulans
that
vezatin
homolog
VezA
is
important
assembly.
affects
microtubule
plus-end
accumulation
of
dynein
before
adapter-mediated
activation,
two
processes
both
need
dynactin.
The
contains
multiple
components
including
an
Arp1
(actin-related
protein
1)
mini-filament
associated
with
a
pointed-end
sub-complex.
physically
interacts
either
directly
or
indirectly
via
its
Loss
causes
defect
integrity,
most
likely
by
affecting
connection
between
Using
various
mutants,
further
revealed
must
be
highly
coordinated.
Together,
these
results
shed
new
light
on
vivo.
Molecular Neurobiology,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 31, 2024
Abstract
Molecular
motors
are
cellular
components
involved
in
the
intracellular
transport
of
organelles
and
materials
to
ensure
cell
homeostasis.
This
is
particularly
relevant
neurons,
where
synaptic
synthesized
soma
need
travel
over
long
distances
their
destination.
They
can
walk
on
microtubules
(kinesins
dyneins)
or
actin
filaments
(myosins),
major
cytoskeleton.
While
kinesins
mostly
perform
anterograde
toward
plus
ends
located
distally
processes,
cytoplasmic
dyneins
allow
retrograde
flux
cargo
minus
at
soma.
Axon
myelination
represents
a
aspect
neuronal
maturation
essential
for
function,
as
it
speeds
up
transmission
electrical
signals.
Increasing
evidence
supports
role
molecular
homeostatic
control
myelination.
includes
trafficking
myelin
along
processes
myelinating
cells
local
regulation
pathways
that
axon
wrapping.
Dysfunctional
machinery
has
therefore
been
linked
several
brain
pathologies,
including
demyelinating
diseases.
These
disorders
include
broad
spectrum
conditions
characterized
by
pathological
demyelination
axons
within
nervous
system,
ultimately
leading
axonal
degeneration
death,
with
multiple
sclerosis
representing
most
prevalent
studied
condition.
review
highlights
involvement
It
also
discusses
studies
have
yielded
insights
into
dysfunctional
activity
pathophysiology
sclerosis.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 6, 2024
ABSTRACT
The
endoplasmic
reticulum
(ER)
relies
on
the
microtubule
cytoskeleton
for
distribution
and
re-modelling
of
its
extended
membrane
network,
but
how
microtubule-based
motors
contribute
to
ER
organization
remains
unclear.
Using
biochemical
cell-based
assays,
we
identify
cerebellar
degeneration-related
protein
2
(CDR2)
paralog
CDR2-like
(CDR2L),
onconeural
antigens
with
poorly
understood
functions,
as
adaptors
cytoplasmic
dynein-1
(dynein).
We
demonstrate
that
CDR2
is
recruited
by
integral
kinectin
(KTN1)
double
knockout
CDR2L
enhances
KTN1-dependent
sheet
stacking,
reversal
which
exogenous
requires
dynein-binding
CC1
box
motif.
Exogenous
expression
additionally
promotes
box-dependent
clustering
sheets
near
centrosomes.
competes
eEF1Bβ
subunit
translation
elongation
factor
1
binding
KTN1,
knockdown
increases
endogenous
levels
sheets,
inducing
their
centrosome-proximal
clustering.
Our
study
describes
a
novel
molecular
pathway
implicates
dynein
in
may
be
involved
pathogenesis
paraneoplastic
degeneration.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 30, 2024
Dynein-1
is
a
microtubule
motor
responsible
for
the
transport
of
cytoplasmic
cargoes.
Activation
motility
requires
it
first
overcome
an
autoinhibited
state
prior
to
its
assembly
with
dynactin
and
cargo
adaptor.
Studies
suggest
that
Lis1
may
relieve
dynein’s
state.
However,
evidence
this
mechanism
lacking.
We
set
out
determine
rules
governing
dynein-Lis1
binding,
which
reveals
their
binding
affinity
regulated
by
nucleotide-bound
states
each
three
nucleotide-binding
pockets
within
dynein
domain.
also
find
distinct
nucleotide
‘codes’
coordinate
stoichiometry
impacting
at
two
different
sites
Electron
microscopy
1
Lis1:1
complex
directly
promotes
open,
uninhibited
conformational
dynein,
whereas
2:1
resembles
Cryo-EM
analysis
structural
basis
opening
relies
on
interactions
linker
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Апрель 20, 2024
Abstract
Cytoplasmic
dynein-mediated
intracellular
transport
needs
the
multi-component
dynactin
complex
for
cargo
binding
and
motor
activation.
However,
cellular
factors
involved
in
assembly
remain
unexplored.
Here
we
found
Aspergillus
nidulans
that
vezatin
homolog
VezA
is
important
assembly.
affects
microtubule
plus-end
accumulation
of
dynein
before
adapter-mediated
activation,
two
processes
both
need
dynactin.
The
contains
multiple
components
including
an
Arp1
(actin-related
protein
1)
mini-filament
associated
with
a
pointed-end
sub-complex.
physically
interacts
either
directly
or
indirectly
via
its
Loss
causes
defect
integrity,
most
likely
by
affecting
connection
between
Using
various
mutants,
further
revealed
must
be
highly
coordinated.
Together,
these
results
shed
new
light
on
vivo.
Cytoplasmic
dynein-mediated
intracellular
transport
needs
the
multi-component
dynactin
complex
for
cargo
binding
and
motor
activation.
However,
cellular
factors
involved
in
assembly
remain
unexplored.
Here
we
found
Aspergillus
nidulans
that
vezatin
homolog
VezA
is
important
assembly.
affects
microtubule
plus-end
accumulation
of
dynein
before
adapter-mediated
activation,
two
processes
both
need
dynactin.
The
contains
multiple
components
including
an
Arp1
(actin-related
protein
1)
mini-filament
associated
with
a
pointed-end
sub-complex.
physically
interacts
either
directly
or
indirectly
via
its
Loss
causes
defect
integrity,
most
likely
by
affecting
connection
between
Using
various
mutants,
further
revealed
must
be
highly
coordinated.
Together,
these
results
shed
new
light
on
vivo.