Nature Communications,
Год журнала:
2022,
Номер
13(1)
Опубликована: Дек. 19, 2022
Abstract
Acutely
silencing
specific
neurons
informs
about
their
functional
roles
in
circuits
and
behavior.
Existing
optogenetic
silencers
include
ion
pumps,
channels,
metabotropic
receptors,
tools
that
damage
the
neurotransmitter
release
machinery.
While
former
hyperpolarize
cell,
alter
ionic
gradients
or
cellular
biochemistry,
latter
allow
only
slow
recovery,
requiring
de
novo
synthesis.
Thus,
combining
fast
activation
reversibility
are
needed.
Here,
we
use
light-evoked
homo-oligomerization
of
cryptochrome
CRY2
to
silence
synaptic
transmission,
by
clustering
vesicles
(SVs).
We
benchmark
this
tool,
optoSynC,
Caenorhabditis
elegans
,
zebrafish,
murine
hippocampal
neurons.
optoSynC
clusters
SVs,
observable
electron
microscopy.
Locomotion
occurs
with
tau
on
~7.2
s
recovers
off
~6.5
min
after
light-off.
can
inhibit
exocytosis
for
several
hours,
at
very
low
light
intensities,
does
not
affect
currents,
biochemistry
proteins,
may
further
manipulating
different
SV
pools
transfer
SVs
between
them.
Current Opinion in Pharmacology,
Год журнала:
2022,
Номер
63, С. 102192 - 102192
Опубликована: Март 4, 2022
The
field
of
photopharmacology
Class
A
GPCR
ligands
has
recently
attracted
attention.
In
this
review
we
analyze
31
papers
on
currently
available
photoswitchable
for
GPCRs.
Using
the
six
most
recurring
terms
all
combined
paper
abstracts,
one
can
extract
overarching
goal
area
research:
"Photoswitchable
control
receptor
activity
with
light"
(represented
in
TOC
graphic).
We
design,
photochemistry
and
pharmacology
ligands.
Trends,
challenges
limitations
will
be
discussed.
number
efficient
that
allow
optical
modulation
function
various
vitro
assays
are
presented.
Moreover,
vivo
is
within
reach
first
reports
to
end
highlighted.
Frontiers in Chemistry,
Год журнала:
2022,
Номер
10
Опубликована: Июнь 22, 2022
The
first
member
and
eponym
of
the
rhodopsin
family
was
identified
in
1930s
as
visual
pigment
rod
photoreceptor
cell
animal
retina.
It
found
to
be
a
membrane
protein,
owing
its
photosensitivity
presence
covalently
bound
chromophoric
group.
This
group,
derived
from
vitamin
A,
appropriately
dubbed
retinal.
In
1970s
microbial
counterpart
this
species
discovered
an
archaeon,
being
protein
also
harbouring
retinal
chromophore,
named
bacteriorhodopsin.
Since
their
discovery
photogenic
panorama
unfolded,
where
up
date
new
members
subspecies
with
variety
light-driven
functionality
have
been
added
family.
branch,
meanwhile
categorized
type-2
rhodopsins,
turned
out
form
large
subclass
superfamily
G
protein-coupled
receptors
are
essential
multiple
elements
light-dependent
sensory
physiology.
type-1
largely
function
ion
pumps
or
channels,
but
contain
sensory-active
enzyme-sustaining
subspecies.
review
we
will
follow
development
exciting
representative
number
highlights
present
prospect
extraordinary
future
potential.
Proceedings of the National Academy of Sciences,
Год журнала:
2023,
Номер
120(21)
Опубликована: Май 15, 2023
Animal
opsins,
light-sensitive
G
protein-coupled
receptors,
have
been
used
for
optogenetic
tools
to
control
protein-dependent
signaling
pathways.
Upon
protein
activation,
the
Gα
and
Gβγ
subunits
drive
different
intracellular
pathways,
leading
complex
cellular
responses.
For
some
purposes,
Gα-
Gβγ-dependent
needs
be
separately
modulated,
but
these
responses
are
simultaneously
evoked
due
1:1
stoichiometry
of
Nevertheless,
we
show
temporal
activation
using
a
self-inactivating
invertebrate
opsin,
Platynereis
c-opsin1,
drives
biased
GIRK
channel
in
light-dependent
manner
by
utilizing
kinetic
difference
between
Gα-dependent
The
opsin-induced
transient
Gi/o
preferentially
causes
kinetically
fast
channels
rather
than
slower
Gi/oα-dependent
adenylyl
cyclase
inhibition.
Although
similar
Gβγ-biased
properties
were
observed
vertebrate
visual
pigment,
c-opsin1
requires
fewer
retinal
molecules
evoke
Furthermore,
enhanced
genetically
fusing
with
RGS8
protein,
which
accelerates
inactivation.
opsin
its
RGS8-fusion
can
function
as
optical
ion
modulation.
Nature Communications,
Год журнала:
2022,
Номер
13(1)
Опубликована: Дек. 19, 2022
Abstract
Acutely
silencing
specific
neurons
informs
about
their
functional
roles
in
circuits
and
behavior.
Existing
optogenetic
silencers
include
ion
pumps,
channels,
metabotropic
receptors,
tools
that
damage
the
neurotransmitter
release
machinery.
While
former
hyperpolarize
cell,
alter
ionic
gradients
or
cellular
biochemistry,
latter
allow
only
slow
recovery,
requiring
de
novo
synthesis.
Thus,
combining
fast
activation
reversibility
are
needed.
Here,
we
use
light-evoked
homo-oligomerization
of
cryptochrome
CRY2
to
silence
synaptic
transmission,
by
clustering
vesicles
(SVs).
We
benchmark
this
tool,
optoSynC,
Caenorhabditis
elegans
,
zebrafish,
murine
hippocampal
neurons.
optoSynC
clusters
SVs,
observable
electron
microscopy.
Locomotion
occurs
with
tau
on
~7.2
s
recovers
off
~6.5
min
after
light-off.
can
inhibit
exocytosis
for
several
hours,
at
very
low
light
intensities,
does
not
affect
currents,
biochemistry
proteins,
may
further
manipulating
different
SV
pools
transfer
SVs
between
them.
