addition
found
cdk5
involved
bdnf-induced
activation
rho
gtpase
cdc42
essential
bdnf-triggered
dendritic
growth
observations
therefore
reveal
unanticipated
role
cdk5
trkb-mediated
regulation
dendritic
growth
modulation
bdnf-induced
cdc42
activation
rho
gtpases
including
rhoa
rac1
cdc42
key
regulators
actin
cytoskeleton
dynamics
since
bdnf
stimulation
observed
activate
rac1
cdc42
neurons
interested
delineate
rho
gtpases
contribute
bdnf-stimulated
dendritic
growth
investigate
rho
gtpases
involved
identify
rho
gtpase
implicated
hippocampal
neurons
transfected
wt
dn
rac1
cdc42
rhoa
found
overexpression
wt
dn
rac1
increased
basal
number
dendrites
absence
bdnf
treatment
overexpression
both
forms
rac1
abolished
bdnf-stimulated
dendritic
growth
other
hand
overexpression
dn
rhoa
slightly
enhanced
primary
dendrites
irrespective
bdnf
stimulation
overexpression
both
wt
dn
forms
rhoa
inhibited
bdnf-stimulated
dendritic
growth
remarkably
contrast
inhibition
bdnf-stimulated
dendritic
growth
cells
overexpressing
wt
rac1
rhoa
bdnf
stimulation
hippocampal
neurons
overexpressing
wt
cdc42
resulted
increase
primary
dendrites
nearly
abolished
overexpression
dn
cdc42
figure
6a
observations
therefore
suggest
rac1
rhoa
may
also
modulate
bdnf-stimulated
dendritic
growth
activation
cdc42
following
bdnf
stimulation
most
likely
mediates
increase
primary
dendrites
bdnf
current
study
demonstrated
ser478
phosphorylation
trkb
cdk5
essential
cdc42-dependent
increase
primary
dendrites
triggered
bdnf
thus
adding
new
regulatory
component
mechanisms
involved
rho
gtpase
activation
neurotrophin
although
precise
downstream
pathways
phosphorylation
affects
cdc42
activation
remains
determined
observations
provide
interesting
insights
gtpase
activity
measured
described
briefly
cultured
cortical
neurons
div7
pretreated
dmso
ros
min
followed
treatment
bdnf
another
min
cells
lysed
incubated
pak1-pbd
agarose
constant
rocking
h.
proteins
bound
beads
washed
three
times
lysis
buffer
eluted
sds
sample
buffer
analyzed
bound
cdc42
western
blotting
using
monoclonal
antibody
against
cdc42
upstate
biotechnology
gtpase
activity
quantified
densitometry
analysis
blotsinterestingly
appl1
bind
rab21
gtp-dependent
manner
figure
indicating
appl1
effector
both
rab5
rab21
gtpase
binding
emerged
major
function
ph
domains
addition
lipid
binding
lemmon
example
ph
domains
guanine
nucleotide-exchange
factors
gef
shown
bind
directly
cognate
small
gtpases
rossman
et
al
lu
et
al
data
now
show
direct
interaction
between
appl1
ph
domain
rab5
far
only
two
crystal
structures
small
gtpase
ph
domain
complexes
available
one
ran
ranbd1
pdb
file
1rrp
interactions
between
ran
gtpase
domain
ranbd1
ph
core
domain
fairly
minor
occurring
between
switch
region
gtpase
equivalent
rab5
strand
ph
domain
interaction
alone
unlikely
sufficient
form
stable
complex
indeed
ran
long
c-terminal
peptide
beside
gtpase
domain
ph
domain
ranbd1
extra
n-terminal
peptide
two
terminal
peptides
wrap
around
partner
proteins
forming
major
interaction
between
ran
ranbd1
such
interaction
seems
required
rab5
appl1
gtpase
domain
rab5
bar-ph
domain
appl1
sufficient
mediate
interaction
second
published
small
gtpase
ph
complex
ral
exo84
pdb
file
1zc3
complex
ph
domain
exo84
uses
l1
l6
interact
interswitch
switch
ii
regions
ral
forming
intermolecular
β-sheet
extension
mediated
ph
strand
gtpase
strand
jin
et
al
mutagenesis
analysis
points
different
surface
region
l3
ph
domain
rab5
binding
therefore
rab5
appl1
interaction
represents
new
gtpase
ph
binding
mode