# Presentation: 881973

## Cadherin--catenin Adhesion Complexes 

***Cadherin-************-catenin Adhesion Complexes ***
***in Synaptic Development and Remodeling***

***Shernaz X. Bamji***
**University of British Columbia**
_**2006 NIDA Frontiers in Addiction Mini-Convention**_

## Cadherin Superfamily

**Desmosomal**

- DP

**Protocadherin**

- Fyn

**Seven-Pass Tm **

- flamingo
- starry night

- desmocollin

- desmoglein

- CNR-cadherin

- PCDH8/ arcadlin

- FAT-family

- DP

- T-cadherin

**FAT-like **

**Unique**

**Classic**

**I**

**II**

**III**

**IV**

**V**

**VI**

- Adapted from : Angst et al., J.Cell Sci. 114:629

- F-actin

- -cat

- -cat

## Synaptic localization of cadherin and catenin

**active zone**

**PRESYNAPTIC**

**POSTSYNAPTIC**

- Uchida et al. 1996.  JCB. 135:767-779

## Synapse number and structure is altered in -catenin mutant mice

- -catenin mutant

- vesicles / synapse

- 0

- 5

- 10

- 15

- 20

- 25

******

- WT

- MT

- docked

- vesicle cluster

- Synapse number and structure is altered in -catenin mutant mice

- synapses /1000 m2

- WT

- MT

- 0

- 100

- 200

- 300

- 400

******

## **

- Synaptic vesicles are diffusely localized when -catenin is ablated

- Synaptophysin-GFP

- +/+

- -/-

- Length of syn-GFP
- major axis  (m)

- 0

- 1

- 2

- 3

******

- +/+

- -/-

- -/-

##   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?**

## There is an Increase in SV Cluster Splitting Following BDNF Treatment

- Rate : 1 frame/ 5 sec

- 2 m

## BDNF increases the density of synaptophysin-GFP puncta

- Syn-GFP

- Syn-GFP

- _control_

- _BDNF_

## BDNF mediates cadherin--catenin uncoupling

- BDNF mediates cadherin--catenin uncoupling

- BDNF

- Ø

- 10’

- 30’

- IP: -catenin

- P-tyr

- N-cadherin

- -catenin

## **

- 0

- 50

- 100

- 150

- 200

******

- BDNF

- Syn-GFP

- Syn-GFP

- +Y654F

- Percent synapse density
- (Synaptophysin-GFP)

- 0

- 0.05

- 0.04

- 0.02

- 0.01

- Y654F

- 0.06

- 0.03

- Ave freq of splitting
- (synapse -1 X min -1)

- Syn-GFP

- Syn-GFP

- 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

## Slide 12

## Slide 13

## Slide 14

## Slide 15

## Synaptic vesicles associated with one synapse split to form new synapses and to associate with existing synapses

- Synaptophysin-PS-CFP
- PSD-95

- Synaptophysin-PS-CFP
- Synaptophysin-RFP

## Acknowledgements

_*Louis F. Reichardt*_
* *
*(University of California San Francisco*
*San Francisco, CA)*

- Nikole Kimes

_*Shernaz X. Bamji*_

- Lucia Tapia
- Eileen Yoshida
- Yu Sun
*(University of British Columbia*
*Vancouver, B.C.)*

- Tula Foundation
- Michael Smith Foundation for Health Research
- Canadian Institutes of Heath Research (CIHR)
- Canadian Foundation for Innovation
- British Columbia Knowledge Development Fund

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## Slide 19