Lecture 12: Post-Synaptic Density

Question 1

Post-synaptic specialisation includes…

Answer 1

Ligand-gated ion channels, anchoring proteins, cytoskeleton and regulatory proteins

Question 2

Why is it called Post-synaptic “Density”?

Answer 2

It appears dense on the electron micrograph

Question 3

True or False: inhibitory synapses have a larger variety of different proteins than excitatory.

Answer 3

False. Inhibitory synapses have at least 250 different proteins. Excitatory synapses have more than 1000 different proteins

Question 4

Mutations in the _____ protein are associated with autism and schizophrenia.

Answer 4

SHANK proteins. Mutations in SHANK signal back across the synaptic cleft through neuroligin via neurexin into the release mechanisms on the presynaptic side.

Question 5

Define: Neuroligins and what they bind to

Answer 5

Post-synaptic cell adhesion molecules that bind across synaptic cleft to neurexins. Neuroligins bind to PSD95 via the third PDZ domain

Question 6

Neuroligin 1 is characteristically found in all _____ synapses

Answer 6

Glutamatergic and some nicotinic synapses in the PNS. Typically neuroligin 1 and neuroligin 2 are not found together

Question 7

Neuroligin 2 found preferentially in _____ synapses

Answer 7

some inhibitory GABAtergic synapses

Question 8

Neuroligin 3 is found in _____ synapses

Answer 8

inhibitory and excitatory synapses. Forms heterodimers with neuroligin 1

Question 9

Neuroligin 4 is found in _____ synapses

Answer 9

Found preferentially at inhibitory glycinergic synapses in the retina

Question 10

PSD95 is also called….

Answer 10

SAP 90 (synapse-associated protein 90) and DLG4 (Disks Large Homologue 4)

Question 11

PSD95 has how many PDZ binding domains?

Answer 11

3

Question 12

How large is the PDZ binding domain motif

Answer 12

80-90 amino acids

Question 13

PSD binds AMPA glutamate receptors via the ____.

Answer 13

1st PDZ binding domain

Question 14

Function of SHANK proteins

Answer 14

Cytoskeletal proteins that bind to actin cytoskeleton via cortactin.
Shank proteins are multidomain scaffold proteins of the postsynaptic density that connect neurotransmitter receptors, ion channels, and other membrane proteins to the actin cytoskeleton and G-protein-coupled signaling pathways.
Shank proteins also play a role in synapse formation and dendritic spine maturation.
Mutations in SHANK signal back across the synaptic cleft through neuroligin via neurexin into the release mechanisms on the presynaptic side

Question 15

PSD95 binds to….

Answer 15

Neuroligins
AMPA receptors
NDMA receptors
Calcium-calmodulin protein kinase II (CaMKII) which regulates NMDA and AMPA cycling and is implicated in memory formation. Targets include proteins that insert AMPA and NMDA receptors into the membrane.
Neuronal nitric oxide synthase implicated in synaptic plasticity and neuroprotection
Shank proteins, indirectly via GKAP. Shanks can also bind directly to neuroligins.

Question 16

Shank proteins bind to

Answer 16

metabotropic glutamate receptors via Homer

IP3 receptors on the smooth ER via Homer

Question 17

What is the key organising molecule specific for inhibitory synapses such as GABA and glycine

Answer 17

Gephyrin