METHODS OF ACQUIRING KNOWLEDGE IN NURSING.pptx by navdeep kaur
Taisuke tomita
1. 1 121101 Alzforum webinar
Activity-dependent cleavage of Neuroligin 1
Taisuke Tomita
Graduate School of Pharmaceutical Sciences,
The University of Tokyo
2. 2
Neuroligin/Neurexin system
Neuroligin 1 (NLG1) is a
postsynaptic molecule involved
in synaptogenesis.
Aberrant expression of NLG1
has been implicated in the
pathogenesis of Autism
spectrum disorder.
Little information had been
available regarding the
regulation of protein levels of
NLG1.
3. 3
Sequential cleavage of NLG1
in vitro and in vivo
Rat brain Primary neuron
DAPT
TAPI2 NLG1 sNLG1
Medium sNLG1 ADAM10
NLG1-FL
Lysate NLG1-CTF
III-tubulin CTF ICD
-secretase
4. 4
Sequential cleavage of NLG1
in vitro and in vivo
NLG1 sNLG1
ADAM10
CTF ICD
Decreased shedding in ADAM10 cKO brain
-secretase
5. 5
Activity dependent processing of NLG1
in vitro and in vivo
pilocarpine
a.u.
Status Epilepsy (SE)
Soluble
fraction
sNLG1 NLG1
Membrane
cerebrum fraction
6. 6
Inhibition of proteolytic processing of NLG1
increased the synaptogenesis
mock NLG1-FL
7. 7
Inhibition of proteolytic processing of NLG1
increased the synaptogenesis
8. 8
Inhibitory modulation of
synaptogenic activity of Neuroligin by proteolysis
sNRX
Synaptic loss?
NX Neuroligin
Synaptic ADAM10
CTF -secretase
activity Activate!
NMDA
receptor FL CTF
PSD-95 PSD-95 PSD-95
ICD
9. 9
Summary
Neuroligin 1 is sequentially cleaved by ADAM10 and -
secretase.
Shedding of neuroligin 1 is modulated by neuronal
activity and ligand binding.
Neuroligin 1 cleavage is upregulated by epileptic
seizure condition in vivo.
Proteolytic processing of neuroligin 1 negatively
regulates spine formation.