bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Окт. 27, 2023
Abstract
Cells
can
be
described
as
active
composite
materials.
The
mechanical
properties
of
cells
are
controlled
by
complex
polymer
networks
and
dynamically
tuned
for
diverse
cellular
processes
driven
force-generating
motor
proteins.
Microtubules
the
most
rigid
protein
polymers
in
cytoskeleton,
their
material
have
been
measured
vitro
bending
or
analyzing
thermal
fluctuations.
Microtubule
mechanics
living
extremely
difficult
to
probe
directly,
while
fluctuations
interpret
because
they
generated
forces
a
surrounding
cytoplasm
with
poorly
understood
properties.
Here
we
introduce
method
measure
elastic
microtubules
making
use
motor-generated
that
drive
Bending
dynamics
governed
three
main
factors:
microtubule
properties,
cytoskeletal
forces,
response
characteristics
cytoplasm.
We
show
theoretically
that,
when
one
factor
independently
determined,
other
two
derived
from
observed
Using
this
discovered
polyglutamylation,
post-translational
modification
enriched
on
arrays
need
withstand
large
such
those
axons
cilia,
increases
stiffness
cells.
Our
work
provides
theoretical
experimental
framework
study
regulation
tubulin
modifications
effectors
environments.
approach
extended
aspect
ratio
structures
endoplasmic
reticulum
mitochondrial
network.
Annual Review of Cell and Developmental Biology,
Год журнала:
2023,
Номер
39(1), С. 331 - 361
Опубликована: Окт. 16, 2023
Microtubules
are
essential
dynamic
polymers
composed
of
α/β-tubulin
heterodimers.
They
support
intracellular
trafficking,
cell
division,
cellular
motility,
and
other
processes.
In
many
species,
both
α-tubulin
β-tubulin
encoded
by
multiple
genes
with
distinct
expression
profiles
functionality.
further
diversified
through
abundant
posttranslational
modifications,
which
added
removed
a
suite
enzymes
to
form
complex,
stereotyped
arrays.
The
genetic
chemical
diversity
tubulin
constitute
code
that
regulates
intrinsic
microtubule
properties
is
read
effectors,
such
as
molecular
motors
microtubule-associated
proteins,
provide
spatial
temporal
specificity
microtubules
in
cells.
this
review,
we
synthesize
the
rapidly
expanding
literature
highlight
limitations
opportunities
for
field.
As
complex
arrays
underlie
physiological
processes,
better
understanding
how
cells
employ
has
important
implications
human
disease
ranging
from
cancer
neurological
disorders.
The EMBO Journal,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 15, 2025
Elongator
is
a
tRNA-modifying
complex
that
regulates
protein
translation.
Recently,
moonlighting
function
of
has
been
identified
in
regulating
the
polarization
microtubule
cytoskeleton
during
asymmetric
cell
division.
induces
symmetry
breaking
anaphase
midzone
by
selectively
stabilizing
microtubules
on
one
side
spindle,
contributing
to
downstream
polarized
segregation
cell-fate
determinants,
and
therefore
fate
determination.
Here,
we
investigate
how
controls
dynamics.
binds
both
tip
free
GTP-tubulin
heterodimers
using
two
different
subcomplexes,
Elp123
Elp456,
respectively.
We
show
these
activities
must
be
coupled
for
decrease
tubulin
critical
concentration
elongation.
As
consequence,
increases
growth
speed
decreases
catastrophe
rate
microtubules.
Surprisingly,
Elp456
subcomplex
tails
strong
selectivity
towards
polyglutamylated
tubulin.
Hence,
assembled
become
enriched
with
tubulin,
as
observed
vitro,
mouse
Drosophila
lines,
well
vivo
Sensory
Organ
Precursor
cells.
Therefore,
rewrites
code
growing
microtubules,
placing
it
at
core
cytoskeletal
dynamics
Cell Cycle,
Год журнала:
2025,
Номер
unknown, С. 1 - 20
Опубликована: Апрель 22, 2025
Microtubules
are
polymers
of
α/β
tubulin
dimers
that
build
the
mitotic
spindle,
which
segregates
duplicated
chromosomes
during
cell
division.
Microtubule
function
is
governed
by
dynamic
instability,
whereby
cycles
growth
and
shrinkage
contribute
to
forces
necessary
for
chromosome
movement.
Regulation
microtubule
velocity
requires
cycle-dependent
changes
in
expression,
localization
activity
microtubule-associated
proteins
(MAPs)
as
well
post-translational
modifications
modulate
dynamics.
It
has
become
clear
optimal
velocities
required
proper
segregation
ploidy
maintenance.
Suboptimal
rates
can
result
from
altered
MAPs
could
lead
aneuploidy,
possibly
disrupting
establishment
bundles
at
kinetochores
altering
mechanical
sister
chromatid
segregation.
Future
work
using
high-resolution,
low-phototoxicity
microscopy
novel
fluorescent
markers
will
be
invaluable
obtaining
deeper
mechanistic
insights
into
how
processes
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Март 12, 2024
Abstract
Developmental
remodeling
shapes
neural
circuits
via
activity-dependent
pruning
of
synapses
and
axons.
The
cytoskeleton
is
critical
for
this
process,
as
microtubule
loss
enzymatic
severing
an
early
step
across
many
species.
However,
how
microtubule-severing
enzymes,
such
spastin,
are
activated
in
specific
neuronal
compartments
remains
unknown.
Here,
we
reveal
that
polyglutamylation,
a
posttranslational
tubulin
modification
enriched
neurons,
plays
instructive
role
developmental
by
tagging
microtubules
severing.
Motor
neuron-specific
gene
deletion
enzymes
add
or
remove
polyglutamylation—TTLL
glutamylases
vs.
CCP
deglutamylases—accelerates
delays
neuromuscular
synapse
neurotransmission-dependent
manner.
This
mechanism
not
to
peripheral
but
also
operates
central
circuits,
e.g.,
the
hippocampus.
Thus,
polyglutamylation
acts
rheostat
morphology
connectivity.
Tubulin
glutamylation
is
a
reversible
modification
of
the
microtubules
that
regulates
cilia
stability
and
function.
The
addition
glutamates
to
microtubule
catalyzed
by
members
TTLL
family
enzymes,
while
removal
carried
out
cytosolic
carboxypeptidase
(CCP)
enzymes.
C.
elegans
has
two
deglutamylating
CCPP-1
CCPP-6
.
required
for
ciliary
function
in
worm,
however
dispensable
integrity.
To
investigate
redundancy
between
enzymes
we
made
ccpp-1
(
ok1821
);
ccpp-6
ok382
)
double
mutant.
mutant
shows
normal
viability,
dye-filling
phenotypes
are
not
worse
than
single
mutant,
suggesting
do
redundantly
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Май 10, 2023
Elongator
is
a
tRNA-modifying
complex
that
regulates
the
fidelity
of
protein
translation.
Recently,
moonlighting
function
has
been
identified
in
regulating
polarization
microtubule
cytoskeleton
during
asymmetric
cell
division.
induces
symmetry
breaking
anaphase
midzone
by
selectively
stabilizing
microtubules
on
one
side
spindle.
This
polarizes
segregation
signalling
endosomes
containing
cell-fate
determinants
to
only
daughter
cell,
thus
contributing
fate
determination.
Here,
we
unravelled
molecular
mechanism
which
controls
dynamics.
binds
simultaneously
tip
and
also
free
GTP-tubulin
heterodimers
via
their
C-terminal
tails.
thereby
locally
increases
tubulin
concentration
at
ends,
stabilizes
increasing
growth
speed
decreasing
catastrophe
rate.
We
show
Elp123
Elp456
subcomplexes
bind
heterodimers,
respectively,
these
activities
must
be
coupled
for
stabilize
microtubules.
Surprisingly,
found
strong
selectivity
towards
polyglutamylated
dimers.
Hence,
assembled
become
enriched
with
tubulin.
Therefore,
can
rewrite
code
growing
microtubules,
placing
it
core
cytoskeletal
dynamics
Abstract
Glutamylation
yields
N
‐functionalized
amino
acids
in
several
natural
pathways.
γ‐Glutamylated
may
exhibit
improved
properties
for
their
industrial
application,
e.
g.,
as
taste
enhancers
or
peptide
drugs.
γ‐Glutamyl−isopropylamide
(GIPA)
can
be
synthesized
from
isopropylamine
(IPA)
and
l
‐glutamate.
In
Pseudomonas
sp.
strain
KIE171,
GIPA
is
an
intermediate
the
biosynthesis
of
‐alaninol
(2‐amino‐1‐propanol),
a
precursor
fluorochinolone
antibiotic
levofloxacin
chloroacetanilide
herbicide
metolachlor.
this
study,
fermentative
production
with
metabolically
engineered
putida
KT2440
using
γ‐glutamylmethylamide
synthetase
(GMAS)
Methylorubrum
extorquens
was
established.
Upon
addition
IPA
during
growth
glycerol
carbon
source
shake
flasks,
recombinant
produced
up
to
21.8
mM
GIPA.
fed‐batch
bioreactor
cultivations,
accumulated
titer
11
g
L
−1
product
yield
0.11
volumetric
productivity
0.24
h
.
To
best
our
knowledge,
first