γ-TuRC asymmetry induces local protofilament mismatch at the RanGTP-stimulated microtubule minus end
The EMBO Journal,
Год журнала:
2024,
Номер
43(10), С. 2062 - 2085
Опубликована: Апрель 10, 2024
The
γ-tubulin
ring
complex
(γ-TuRC)
is
a
structural
template
for
de
novo
microtubule
assembly
from
α/β-tubulin
units.
isolated
vertebrate
γ-TuRC
assumes
an
asymmetric,
open
structure
deviating
geometry,
suggesting
that
closure
may
underlie
regulation
of
nucleation.
Here,
we
isolate
native
γ-TuRC-capped
microtubules
Xenopus
laevis
egg
extract
nucleated
through
the
RanGTP-induced
pathway
spindle
and
determine
their
cryo-EM
structure.
Intriguingly,
minus
end-bound
only
partially
closed
consequently,
emanating
locally
misaligned
with
asymmetric.
In
conformation
γ-TuRC,
actin-containing
lumenal
bridge
destabilised,
modulation
in
microtubule-binding
protein
CAMSAP2
specifically
binds
end
microtubules,
indicating
asymmetric
recruitment
microtubule-modulating
factors
release.
Collectively,
reveal
surprisingly
protofilament
organisation
diverging
regular
structure,
direct
implications
kinetics
nucleation
subsequent
during
assembly.
Язык: Английский
Role of MARK2 in the nervous system and cancer
Cancer Gene Therapy,
Год журнала:
2024,
Номер
31(4), С. 497 - 506
Опубликована: Фев. 2, 2024
Язык: Английский
Centrosomal and acentrosomal microtubule nucleation during neuronal development
Current Opinion in Neurobiology,
Год журнала:
2025,
Номер
92, С. 103016 - 103016
Опубликована: Март 28, 2025
Язык: Английский
Heterogeneous local structures of the microtubule lattice revealed by cryo-ET and non-averaging analysis
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Май 2, 2024
Summary
Microtubule
cytoskeletons
play
pivotal
roles
in
various
cellular
processes,
including
cell
division
and
locomotion,
by
dynamically
changing
their
length
distribution
cells
through
tubulin
polymerization/depolymerization.
Recent
structural
studies
have
revealed
the
polymorphic
lattice
structure
of
microtubules
closely
correlate
with
microtubule
dynamics,
but
were
limited
to
averaged
structures.
To
reveal
transient
localized
structures,
such
as
GTP-cap,
we
developed
several
non-averaging
methods
for
cryogenic
electron
tomography
precisely
measure
longitudinal
spacing
helical
twisting
individual
lattices
at
subunit
level.
Our
analysis
that
polymerizing
depolymerizing
ends
share
a
similar
regards
spacing.
The
most
distinctive
property
specific
plus
end
was
left-handed
inter-dimer
interface,
suggesting
might
accelerate
fast
polymerization
ends.
uncovered
heterogeneity
native
will
be
indispensable
study
dynamics
under
physiological
contexts
or
during
events.
Язык: Английский
Phase separation of microtubule-binding proteins – implications for neuronal function and disease
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.
Язык: Английский