Lecture 9: The Postsynaptic Density Flashcards

1
Q

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

A

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

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2
Q

What does the PSD core consist of?

A

high concentration of PSD-95

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3
Q

What is PSD95 orientated with? What does this suggest?

A

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

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4
Q

What is the PSD pallium?

A

deeper layer, containing a scaffold of Shank and Homer proteins

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5
Q

What happens to the pallium during intense synaptic activity?

A

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

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6
Q

How many proteins do excitatory synapses have in the brain?

A

more than 1000 different proteins

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7
Q

How many proteins do inhibitory synapses have in the brain?

A

at least 250 different proteins

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8
Q

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

A

membrane-associated guanylate kinases

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

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9
Q

What are GKAPs?

A

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

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10
Q

What are SHANKs?

A

SH3 and multiple ankyrin repeat domains protein

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11
Q

What are Homer proteins also called?

A

VesI, cupidin and PSD-Zip45

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12
Q

What are many PSD proteins involved in?

A

cell adhesion

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13
Q

What are many PSD proteins also known as?

A

CAMs (cellular adhesion molecules)

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14
Q

What is a neuroligin?

A

a cell adhesion protein on the postsynaptic membrane

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15
Q

What is a neurexin?

A

a family of presynaptic cell adhesion proteins that have roles in connecting neurons at the synapse

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16
Q

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

A

mostly on the presynaptic membrane and contain a single transmembrane domain

17
Q

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

A

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

18
Q

Where is neuroligin 1 characteristically found?

A

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

19
Q

Where is neuroligin 2 characteristically found?

A

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

20
Q

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

A

in excitatory and inhibitory synapses

heterodimers

21
Q

Where is neuroligin 4 characteristically found?

A

found preferentially at glycinergic synapses in retina

22
Q

What do neuroligins bind to?

A

postsynaptic density protein 95

23
Q

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

A

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

24
Q

How many amino acids in the PDZ motif?

A

80-90 amino acids

25
Q

How do neuroligins bind to PSD95?

A

via 3rd PDZ domain

26
Q

How does PSD95 bind AMPA glutamate receptors?

A

via 1st PDZ domain

27
Q

Which interaction holds AMPA receptors in place?

A

neuroligin/neurexin interaction

28
Q

What are the different things PSD95 bind to?

A

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

29
Q

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

A

via the PDZ domains

30
Q

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

A

via CAMs

major example is the neurexin-neuroligin interaction

31
Q

What happens when neuroligin is deleted?

A

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

32
Q

What do postsynaptic densities include?

A

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

33
Q

What are Shanks?

A

cytoskeletal proteins which couple via contact into the actin cytoskeleton

34
Q

How do Shanks bind to the actin cytoskeleton?

A

bind via Homer to metabotropic glutamate receptors

also via Homer to IP3 receptors on the SER

35
Q

What is gephyrin? What is it specific for?

A

key organising molecule specific for GABA and glycinergic synapses

36
Q

How and what does gephyrin interact with?

A

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

37
Q

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

A

the nicotinic acetylcholine receptor

pentameric transmembrane proteins which contain at least 2 ɑ-subunits