The protein phosphatase 2A holoenzyme is a key regulator of starch metabolism and bradyzoite differentiation in Toxoplasma gondii
Nature Communications,
Год журнала:
2022,
Номер
13(1)
Опубликована: Дек. 8, 2022
Phenotypic
switching
between
tachyzoite
and
bradyzoite
is
the
fundamental
mechanism
underpinning
pathogenicity
adaptability
of
protozoan
parasite
Toxoplasma
gondii.
Although
accumulation
cytoplasmic
starch
granules
a
hallmark
quiescent
stage,
regulatory
factors
mechanisms
contributing
to
amylopectin
storage
in
bradyzoites
are
incompletely
known.
Here,
we
show
that
T.
gondii
protein
phosphatase
2A
(PP2A)
holoenzyme
composed
catalytic
subunit
PP2A-C,
scaffold
PP2A-A
PP2A-B.
Disruption
any
these
subunits
increased
blocked
tachyzoite-to-bradyzoite
differentiation.
PP2A
contributes
regulation
metabolism
via
dephosphorylation
calcium-dependent
kinase
2
at
S679.
Phosphoproteomics
identified
several
putative
substrates
involved
Our
findings
provide
novel
insight
into
role
as
key
regulator
differentiation
Язык: Английский
Converting and hoarding driven by protein phosphorylation in Toxoplasma gondii
Trends in Parasitology,
Год журнала:
2023,
Номер
39(4), С. 232 - 234
Опубликована: Фев. 17, 2023
Язык: Английский
Histone variant H2B.Z acetylation is necessary for maintenance ofToxoplasma gondiibiological fitness
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Фев. 14, 2023
Abstract
Through
regulation
of
DNA
packaging,
histone
proteins
are
fundamental
to
a
wide
array
biological
processes.
A
variety
post-translational
modifications
(PTMs),
including
acetylation,
constitute
proposed
code
that
is
interpreted
by
“reader”
modulate
chromatin
structure.
Canonical
histones
can
be
replaced
with
variant
versions
add
an
additional
layer
regulatory
complexity.
The
protozoan
parasite
Toxoplasma
gondii
unique
among
eukaryotes
in
possessing
novel
H2B
designated
H2B.Z.
combination
PTMs
and
the
use
variants
important
for
gene
T.
gondii,
offering
new
targets
drug
development.
In
this
work,
parasites
were
generated
which
5
N-terminal
acetylatable
lysines
H2B.Z
mutated
either
alanine
(c-Myc-A)
or
arginine
(c-Myc-R).
c-Myc-A
mutant
only
displayed
mild
effect
its
ability
kill
mice.
c-Myc-R
presented
impaired
grow
increase
differentiation
latent
bradyzoites.
This
line
was
also
more
sensitive
damage,
no
virulence
mice,
provided
protective
immunity
against
future
infection.
While
nucleosome
composition
unaltered,
key
genes
abnormally
expressed
during
vitro
bradyzoite
differentiation.
Our
results
show
positive
charge
patch
these
procceses.
Pull
down
assays
acetylated
peptide
unacetylated
one
retrieved
common
differential
interactors.
Acetylated
pulled
associated
chromosome
maintenance/segregation
cell
cycle,
opening
question
possible
link
between
acetylation
status
mitosis.
Язык: Английский
An apicomplexan bromodomain, TgBDP1 associates with diverse epigenetic factors to regulate essential transcriptional processes inToxoplasma gondii
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2022,
Номер
unknown
Опубликована: Дек. 24, 2022
Abstract
The
protozoan
pathogen
Toxoplasma
gondii
relies
on
tight
regulation
of
gene
expression
to
invade
and
establish
infection
in
its
host.
divergent
regulatory
mechanisms
related
apicomplexan
pathogens
rely
heavily
regulators
chromatin
structure
histone
modifications.
important
contribution
acetylation
for
both
acute
chronic
has
been
demonstrated,
where
increases
at
active
loci.
However,
the
direct
consequences
specific
marks
pathway
that
influences
transcriptional
response
modification
is
unclear.
As
a
reader
lysine
acetylation,
bromodomain
serves
as
mediator
between
acetylated
regulators.
Here
we
show
protein
TgBDP1
which
conserved
amongst
Apicomplexa
within
Alveolata
superphylum,
essential
asexual
proliferation.
Using
CUT&TAG
demonstrate
recruited
start
sites
large
proportion
parasite
genes.
Transcriptional
profiling
during
knockdown
revealed
loss
leads
major
dysregulation
expression,
implying
multiple
roles
activation
repression.
This
supported
by
interactome
analysis
demonstrating
forms
core
complex
with
two
other
proteins
an
ApiAP2
factor.
appears
interact
epigenetic
factors
such
nucleosome
remodelling
complexes.
We
conclude
interacts
diverse
exert
opposing
tachyzoite.
Summary
Histone
critical
proper
single
celled
eukaryotic
.
Bromodomain
are
“readers”
may
link
modified
transcription
factors.
Here,
survival
results
global
expression.
promoter
region
genes,
different
key
factor
sensing
modifications
influence
facets
Язык: Английский