Presentation made by Dr. Rui Peixoto, November 1, 2012 on Alzheimer Research Forum (www.alzforum.org)

1. Trans-synaptic signaling by activity dependent cleavage of
Neuroligin-1
Rui T. Peixoto, Portia A. Kunz, Hyungbae Kwon, Angela M. Mabb, Bernardo L. Sabatini,
Benjamin D. Philpot, Michael D. Ehlers
Alzheimer Research Forum Webinar
11/1/2012

2. Activity dependent regulation of Neuroligin-1
GM6001: Broad spectrum Matrix
Metalloprotease Inhibitor

3. NLG1 is cleaved in vivo and in vitro

4. NLG1 cleavage is regulated by activity and mediated by
NMDAR and CaMK signaling

5. NLG1-CTF cleavage is regulated by -secretase activity

6. Activity dependent cleavage of NLG1 is mediated by MMP9

7. NLG1 ectodomain cleavage occurs in the juxtamembrane region

8. NLG1 cleavage is regulated locally and occurs in time scales of minutes

9. Acute NLG1 cleavage reduces mEPSC frequency

10. NLG1 cleavage modulates release probability

11. NLG1 cleavage destabilizes pre-synaptic Neurexin-1

12. Activity dependent NLG1 cleavage in mature and developing circuits

13. NLG1 cleavage:
Homeostatic mechanism
Synaptic/circuit remodeling
Dalva et al. (2007) Nature Neuroscience

14. Neural
Development
NLGs
ASDs Epilepsy
Neurodegeneration
Alzheimer
?