The
sodium
leak
channel
(NALCN)
is
essential
for
survival
in
mammals:
NALCN
mutations
are
life-threatening
humans
and
knockout
lethal
mice.
However,
the
basic
functional
pharmacological
properties
of
have
remained
elusive.
Here,
we
found
that
robust
function
heterologous
systems
requires
co-expression
UNC79,
UNC80,
FAM155A.
resulting
complex
constitutively
active
conducts
monovalent
cations
but
blocked
by
physiological
concentrations
extracellular
divalent
cations.
Our
data
support
notion
directly
responsible
increased
excitability
observed
a
variety
neurons
reduced
Ca2+.
Despite
smaller
number
voltage-sensing
residues
NALCN,
constitutive
activity
modulated
voltage,
suggesting
domains
can
give
rise
to
broader
range
gating
phenotypes
than
previously
anticipated.
work
points
toward
formerly
unknown
contributions
neuronal
opens
avenues
targeting.
Genetics,
Год журнала:
2017,
Номер
205(4), С. 1373 - 1397
Опубликована: Март 30, 2017
The
advantages
of
the
model
organism
Drosophila
melanogaster,
including
low
genetic
redundancy,
functional
simplicity,
and
ability
to
conduct
large-scale
screens,
have
been
essential
for
understanding
molecular
nature
circadian
(∼24
hr)
rhythms,
continue
be
valuable
in
discovering
novel
regulators
rhythms
sleep.
In
this
review,
we
discuss
current
these
interrelated
biological
processes
wider
implications
research.
Clock
genes
period
timeless
were
first
discovered
screens
developed
1970s.
Feedback
on
their
own
transcription
forms
core
clock,
accurately
timed
expression,
localization,
post-transcriptional
modification,
function
is
thought
critical
maintaining
cycle.
Regulators,
several
phosphatases
kinases,
act
different
steps
feedback
loop
ensure
strong
rhythms.
Approximately
150
neurons
fly
brain
that
contain
components
clock
together
translate
intracellular
cycling
into
rhythmic
behavior.
We
how
groups
serve
functions
allowing
clocks
entrain
environmental
cues,
driving
behavioral
outputs
at
times
day,
flexible
responses
conditions.
neuropeptide
PDF
provides
an
important
signal
synchronize
neurons,
although
details
accomplishes
are
still
being
explored.
Secreted
signals
from
also
influence
other
tissues.
SLEEP
is,
part,
regulated
by
which
ensures
appropriate
timing
sleep,
but
amount
quality
sleep
determined
mechanisms
a
homeostatic
balance
between
wake.
Flies
useful
identifying
large
set
genes,
molecules,
neuroanatomic
loci
regulating
amount.
Conserved
aspects
regulation
flies
mammals
include
wake-promoting
roles
catecholamine
neurotransmitters
involvement
hypothalamus-like
regions,
regions
implicated
less
clear
parallels.
Sleep
subject
factors
such
as
food
availability,
stress,
social
environment.
beginning
understand
identified
molecules
interact
with
each
other,
environment,
regulate
researchers
can
take
advantage
increasing
mechanistic
behaviors,
learning
memory,
courtship,
aggression,
loss
impacts
behaviors.
thus
remain
tool
both
discovery
deep
New England Journal of Medicine,
Год журнала:
2021,
Номер
384(6), С. 550 - 561
Опубликована: Фев. 10, 2021
Molecular
insights
into
diurnal
variations
in
human
physiology
and
behavior
are
extending
our
understanding
of
a
wide
range
disease
processes.
Chronobiology
is
also
providing
testable
hypotheses
regarding
the
timing
treatments.
Cold Spring Harbor Perspectives in Biology,
Год журнала:
2017,
Номер
9(1), С. a027706 - a027706
Опубликована: Янв. 1, 2017
Erik
D.
Herzog1,
Tracey
Hermanstyne1,
Nicola
J.
Smyllie2
and
Michael
H.
Hastings2
1Department
of
Biology,
Washington
University
in
St.
Louis,
Missouri
63130-4899
2Division
Neurobiology,
MRC
Laboratory
Molecular
Cambridge
CB2
0QH,
United
Kingdom
Correspondence:
herzog{at}biology2.wustl.edu;
mha{at}mrc-lmb.cam.ac.uk
Science,
Год журнала:
2016,
Номер
351(6276), С. 976 - 981
Опубликована: Фев. 25, 2016
In
Drosophila,
molecular
clocks
control
circadian
rhythmic
behavior
through
a
network
of
~150
pacemaker
neurons.
To
explain
how
the
network's
neuronal
properties
encode
time,
we
performed
brainwide
calcium
imaging
groups
neurons
in
vivo
for
24
hours.
Pacemakers
exhibited
daily
changes
intracellular
Ca(2+)
that
were
entrained
by
environmental
cues
and
timed
clocks.
However,
these
rhythms
not
synchronous,
as
each
group
its
own
phase
activation.
displayed
associated
with
morning
or
evening
locomotor
activities
occurred
~4
hours
before
their
respective
behaviors.
Loss
receptor
neuropeptide
PDF
promoted
synchrony
waves.
Thus,
modulation
is
required
to
sequentially
time
outputs
from
synchronous
pacemakers.
