Peripheral thickening of the sarcomeres and pointed end elongation of the thin filaments are both promoted by SALS and its formin interaction partners
Dávid Farkas,
No information about this author
Szilárd Szikora,
No information about this author
A. S. Jijumon
No information about this author
et al.
PLoS Genetics,
Journal Year:
2024,
Volume and Issue:
20(1), P. e1011117 - e1011117
Published: Jan. 10, 2024
During
striated
muscle
development
the
first
periodically
repeated
units
appear
in
premyofibrils,
consisting
of
immature
sarcomeres
that
must
undergo
a
substantial
growth
both
length
and
width,
to
reach
their
final
size.
Here
we
report
that,
beyond
its
well
established
role
sarcomere
elongation,
Sarcomere
short
(SALS)
protein
is
involved
Z-disc
formation
peripheral
sarcomeres.
Our
localization
data
loss-of-function
studies
Drosophila
indirect
flight
strongly
suggest
radial
initiated
at
Z-disc.
As
thin
filament
used
powerful
nanoscopy
approach
reveal
SALS
subject
major
conformational
change
during
development,
which
might
be
critical
stop
pointed
end
elongation
adult
muscles.
In
addition,
demonstrate
roles
are
dependent
on
formin
type
actin
assembly
factors.
Unexpectedly,
when
present
excess
amounts,
it
promotes
aggregates
highly
resembling
ones
described
nemaline
myopathy
patients.
Collectively,
these
findings
helped
shed
light
complex
mechanisms
coordinated
thickening
sarcomeres,
resulted
discovery
potential
model,
suitable
for
identification
genetic
small
molecule
inhibitors.
Language: Английский
Muscle cofilin alters neuromuscular junction postsynaptic development to strengthen functional neurotransmission
Development,
Journal Year:
2024,
Volume and Issue:
151(13)
Published: June 13, 2024
Cofilin,
an
actin-severing
protein,
plays
key
roles
in
muscle
sarcomere
addition
and
maintenance.
Our
previous
work
found
that
Drosophila
cofilin
(DmCFL)
knockdown
causes
progressive
deterioration
of
structure
function
produces
features
seen
nemaline
myopathy
caused
by
mutations.
We
hypothesized
disruption
actin
cytoskeleton
dynamics
DmCFL
would
impact
other
aspects
development,
and,
thus,
conducted
RNA-sequencing
analysis
unexpectedly
revealed
upregulated
expression
numerous
neuromuscular
junction
(NMJ)
genes.
is
enriched
the
postsynaptic
compartment
F-actin
disorganization
this
subcellular
domain
prior
to
defects
observed
later
development.
Despite
NMJ
gene
changes,
we
no
significant
changes
gross
presynaptic
Bruchpilot
active
zones
or
total
glutamate
receptor
levels.
However,
resulted
mislocalization
GluRIIA
class
receptors
more
deteriorated
muscles
strongly
impaired
transmission
strength.
These
findings
expand
our
understanding
include
structural
development
suggest
may
contribute
pathophysiology
myopathy.
Language: Английский
Muscle cofilin alters neuromuscular junction postsynaptic development to strengthen functional neurotransmission
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Nov. 22, 2023
Abstract
Cofilin,
an
actin
severing
protein,
plays
critical
roles
in
muscle
sarcomere
addition
and
maintenance.
Our
previous
work
has
shown
Drosophila
cofilin
(
DmCFL
)
knockdown
causes
progressive
deterioration
of
structure
function
produces
features
seen
nemaline
myopathy
(NM)
caused
by
mutations.
We
hypothesized
that
disruption
cytoskeleton
dynamics
would
impact
other
aspects
development,
and,
thus,
conducted
RNA
sequencing
analysis
which
unexpectedly
revealed
upregulated
expression
numerous
neuromuscular
junction
(NMJ)
genes.
found
is
enriched
the
postsynaptic
compartment
deficiency
F-actin
disorganization
this
subcellular
domain
prior
to
defects
observed
later
development.
Despite
NMJ
gene
changes,
we
no
significant
changes
gross
presynaptic
Bruchpilot
active
zones
or
total
glutamate
receptor
levels.
However,
results
mislocalization
receptors
containing
GluRIIA
subunit
more
deteriorated
muscles
neurotransmission
strength
strongly
impaired.
These
findings
expand
our
understanding
cofilin’s
include
structural
development
suggest
may
contribute
NM
pathophysiology.
Summary
statement
Cofilin
regulates
organization,
maintenance,
composition,
a
disease
model.
Language: Английский
eEF1α2 is required for actin cytoskeleton homeostasis in the aging muscle
Hidetaka Katow,
No information about this author
Hyung Don Ryoo
No information about this author
Disease Models & Mechanisms,
Journal Year:
2024,
Volume and Issue:
17(9)
Published: Aug. 29, 2024
ABSTRACT
The
translation
elongation
factor
eEF1α
(eukaryotic
1α)
mediates
mRNA
by
delivering
aminoacyl-tRNAs
to
ribosomes.
also
has
other
reported
roles,
including
the
regulation
of
actin
dynamics.
However,
these
distinct
roles
are
often
challenging
uncouple
and
remain
poorly
understood
in
aging
metazoan
tissues.
genomes
mammals
Drosophila
encode
two
paralogs,
with
eEF1α1
expressed
ubiquitously
eEF1α2
expression
more
limited
neurons
muscle
cells.
Here,
we
report
that
plays
a
unique
role
maintaining
myofibril
homeostasis
during
Drosophila.
Specifically,
generated
an
null
allele,
which
was
viable
showed
phenotypes.
In
young
flies,
mutants
had
thinner
myofibrils
indirect
flight
muscles
could
be
rescued
expressing
eEF1α1.
With
aging,
mutant
flies
began
showing
abnormal
distribution
myosin
muscles,
but
without
change
protein
levels.
This
age-related
phenotype
not
overexpression.
These
findings
support
unconventional
myofibers.
Language: Английский