Lecture 9: The Postsynaptic Density

Question 1

Which proteins are clustered immediately opposite release sites or active zones at synapses? What are these proteins known as?

Answer 1

ligand gated ion channels, anchoring proteins, cytoskeleton and regulatory proteins
these proteins are known as density because they appear to be dense in electron microscopy

Question 2

What does the PSD core consist of?

Answer 2

high concentration of PSD-95

Question 3

What is PSD95 orientated with? What does this suggest?

Answer 3

the N-terminus near the plane of postsynaptic membrane and the C-terminus deep in the spine
this close apposition suggests that PSD-95 is in a position to bind neurotransmitter receptors

Question 4

What is the PSD pallium?

Answer 4

deeper layer, containing a scaffold of Shank and Homer proteins

Question 5

What happens to the pallium during intense synaptic activity?

Answer 5

becomes denser and more prominent due to reversible addition of calcium calmodulin, Kinase II and other proteins

Question 6

How many proteins do excitatory synapses have in the brain?

Answer 6

more than 1000 different proteins

Question 7

How many proteins do inhibitory synapses have in the brain?

Answer 7

at least 250 different proteins

Question 8

What are MAGUKs? What is an example of a MAGUK?

Answer 8

membrane-associated guanylate kinases

PSD-95 is the most abundant MAGUK at the mammalian PSD

Question 9

What are GKAPs?

Answer 9

guanylate kinase-associated proteins also known as PSD-95 associated protein

Question 10

What are SHANKs?

Answer 10

SH3 and multiple ankyrin repeat domains protein

Question 11

What are Homer proteins also called?

Answer 11

VesI, cupidin and PSD-Zip45

Question 12

What are many PSD proteins involved in?

Answer 12

cell adhesion

Question 13

What are many PSD proteins also known as?

Answer 13

CAMs (cellular adhesion molecules)

Question 14

What is a neuroligin?

Answer 14

a cell adhesion protein on the postsynaptic membrane that mediates the formation and maintenance of synapses between neurons.

Question 15

What is a neurexin?

Answer 15

a family of presynaptic cell adhesion proteins that have roles in connecting neurons at the synapse - neuroligins act as ligands for Beta-neurexins

Question 16

Where are neurexins located? How many transmembrane domains do they contain?

Answer 16

mostly on the presynaptic membrane and contain a single transmembrane domain

Question 17

What is the role of a neuroligin? What does it act as a ligand for?

Answer 17

mediates the formation and maintenance of synapses between neurons
also act as ligands for β-neurexins, which are cell adhesion proteins located presynaptically

Question 18

Where is neuroligin 1 characteristically found?

Answer 18

in all glutamatergic synapses and some nicotinic synapses in the peripheral nervous system

Question 19

Where is neuroligin 2 characteristically found?

Answer 19

found preferentially in some inhibitory synapses (GABA) and in some cholinergic (acetylcholine) synapses

Question 20

Where is neuroligin 3 characteristically found? What does neuroligin 3 form with neuroligin 1?

Answer 20

in excitatory and inhibitory synapses

heterodimers

Question 21

Where is neuroligin 4 characteristically found?

Answer 21

found preferentially at glycinergic synapses in retina

Question 22

What do neuroligins bind to?

Answer 22

postsynaptic density protein 95

Question 23

How many PDZ binding domains does PSD95 have? What does PDZ mean?

Answer 23

three
P = PSD-95
D = Drosophila disc large tumor suppressor
Z = Zona occludens protein

Question 24

How many amino acids in the PDZ motif?

Answer 24

80-90 amino acids

Question 25

How do neuroligins bind to PSD95?

Answer 25

via 3rd PDZ domain

Question 26

How does PSD95 bind AMPA glutamate receptors?

Answer 26

via 1st PDZ domain

Question 27

Which interaction holds AMPA receptors in place?

Answer 27

neuroligin/neurexin interaction

Question 28

What are the different things PSD95 bind to?

Answer 28

NMDA receptors, calcium-calmodulin protein kinase II, neuronal nitric oxide synthase and shank proteins, indirectly via GKAP

Question 29

How does PSD-95 bind to a number of partners?

Answer 29

via the PDZ domains

Question 30

How do post-synaptic specialisations regulate pre-synaptic specialisations and vice versa? What is a major example?

Answer 30

via CAMs

major example is the neurexin-neuroligin interaction

Question 31

What happens when neuroligin is deleted?

Answer 31

this does not prevent synapse formation as other cell adhesion molecules can substitute

Question 32

What do postsynaptic densities include?

Answer 32

dozens of signal transduction molecules including glutamate receptors, tyrosine kinase receptors and many intracellular signal transduction molecules e.g. protein kinase CaMKII

Question 33

What are Shanks?

Answer 33

cytoskeletal proteins which couple via contact into the actin cytoskeleton

Question 34

How do Shanks bind to the actin cytoskeleton?

Answer 34

bind via Homer to metabotropic glutamate receptors

also via Homer to IP3 receptors on the SER

Question 35

What is gephyrin? What is it specific for?

Answer 35

key organising molecule specific for GABA and glycinergic synapses

Question 36

How and what does gephyrin interact with?

Answer 36

self-assembles into a hexagonal lattice and interacts with various inhibitory synaptic proteins

Question 37

What are both GABA and glycine receptors from the same superfamily as? What are the characteristics of all these receptors?

Answer 37

the nicotinic acetylcholine receptor

pentameric transmembrane proteins which contain at least 2 ɑ-subunits