cadherin- -catenin adhesion complexes in synaptic development and remodeling
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Cadherin--catenin Adhesion Complexes in Synaptic Development and Remodeling
Shernaz X. BamjiUniversity of British Columbia
2006 NIDA Frontiers in Addiction Mini-Convention
Cadherin Superfamily
DesmosomalD
P
Protocadherin
Fyn
Seven-Pass Tm
flamingostarry night
de
smo
colli
n
de
smo
gle
in
CN
R-c
ad
he
rin
PC
DH
8/
arc
ad
lin
FAT-family
DP
T-cadherin
FAT-like
Unique
ClassicI II
III
IV V
VI
Adapted from : Angst et al., J.Cell Sci. 114:629
F-actin
-cat-cat
Type I:N-cadE-cadP-cadR-cadH-cadC-cadDE-cad
Type II:VE-cadK-cadcad-8 to 12cad-18 to 20cad-24
F-actin
-cat-catP
P
active zone
PRESYNAPTIC
POSTSYNAPTIC
Uchida et al. 1996. JCB. 135:767-779
Synaptic localization of cadherin and catenin
control -catenin mutant
vesi
cles
/ sy
nap
se
0
5
10
15
20
25
**
WTMT
docked vesicle cluster
Synapse number and structure is altered in -catenin mutant mice
syn
ap
ses
/1000
m
2
WT MT0
100
200
300
400**
Synaptic vesicles are diffusely localized when -catenin is ablated
Synaptophysin-GFP
+/+ -/-
Leng
th o
f sy
n-
GFP
majo
r axis
(
m)
0
1
2
3
**
+/+ -/-
-/-
/ bassoon
+/+ -/-cadherin
-catenin
-catenin
F-actin
PDZ protein
wnt signaling
Does regulation of cadherin--catenin interactions affect synaptic remodeling and plasticity?
What are the upstream regulators of cadherin--catenin interactions?
What is the function of cadherin in synaptic plasticity?
Rate : 1 frame/ 5 sec 2 m
There is an Increase in SV Cluster Splitting Following BDNF Treatment
Syn-GFP
Syn-GFP
control
BDNF
BDNF increases the density of synaptophysin-GFP puncta
BDNF mediates cadherin--catenin uncoupling
cadherin
-catenin
-catenin
F-actin
PDZ protein
Y654
BDNF Ø 10’ 30’
IP: -catenin
P-tyr
N-cadherin
-catenin
BDNF increases the frequency of synaptic vesicle cluster “splitting” and the density of synapses by disrupting cadherin- -catenin complexes
0
50
100
150
200 **
BDNF
Syn
-GF
P
Syn
-GF
P
+Y
654F
Per
cent
syn
apse
den
sity
(Syn
apto
phys
in-G
FP
)0
0.05
0.04
0.02
0.01
Y65
4F
0.06
0.03
Ave
freq
of s
plitt
ing
(syn
apse
-1 X
min
-1)
Syn
-GF
P
Syn
-GF
P
BDNF
**
BDNF
Conclusions:
Cadherin/ -catenin adhesion complexes are important for localizing SVs to presynaptic compartments during development
Disruption of cadherin/ -catenin adhesion complexes is important for the formation of new synapses
Hypothesis:
Weakening of cadherin/ -catenin complexes enhances synapse formation by increasing the mobility of SV clusters from existing synapses
QuickTime™ and aPhoto - JPEG decompressor
are needed to see this picture.
Synaptic vesicles associated with one synapse split to form new synapses and to associate with existing synapses
Synaptophysin-PS-CFPPSD-95
Synaptophysin-PS-CFPSynaptophysin-RFP
Acknowledgements
Louis F. Reichardt
(University of California San FranciscoSan Francisco, CA)
Nikole Kimes
Shernaz X. Bamji
Lucia TapiaEileen Yoshida
Yu Sun
(University of British ColumbiaVancouver, B.C.)
QuickTime™ and aTIFF (Uncompressed) decompressor
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Tula FoundationMichael Smith Foundation for Health ResearchCanadian Institutes of Heath Research (CIHR)Canadian Foundation for InnovationBritish Columbia Knowledge Development Fund
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