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Molecular and Cellular Neuroscience > The Synapse 1 > Flashcards

The Synapse 1 Flashcards

1
Q

What is the diameter and thickness of the postsynaptic density?

A

300-500nm diameter

50-60 nm thick

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2
Q

Functions of the PSD?

A

Scaffold and regulate receptors

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3
Q

PSD-95 is a protein within the PSD.

Describe its domains N-C terminus

A 
N Terminus (which can dimerise with another psd95 N terminus)
PDZ domains 1-2-3
SH3 domain (allows protein protein interactions)
Guanylate kinase like domain (GUK) which has no enzymes activity
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4
Q

nNOS binds to what pdz domain of psd-95?

A

2

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5
Q

Presynaptic neuroligin bind to what?

A

Pdz 3 and Beta neurexin on presynaptic terminal

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6
Q

How many amino acids in length is a PDZ domain

A

About 100

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7
Q

What does the pdz domain bind to?

A

The C terminus of some protein which have the sequence

X-thr/ser-X-val-COOH

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8
Q

What sequence of amino acids is repeated in pdz domains and why is this important?

A

GLGF

creates hydrophobic pocket for hydrophobic C terminals

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9
Q

Why is arginine important in pdz domains?

A

Arginine at position 318 interacts with COO- via a water molecule

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10
Q

What technique was used to find where NMDAR bind to on psd95?

A

Yeast two hybrid

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11
Q

Who did the experiment to discover where NMDARs bind to in psd-95?

A

Kornau et al 1995

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12
Q

What was the bait in the yeast two hybrid experiment by kornau et al 1995?

A

C terminal of NMDAR

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13
Q

What was the prey in the yeast two experiment by kornau et al 1995?

A

Varying psd-95 constructs

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14
Q

What are the bait and prey attached to? Why is this important?

A

Bait - DNA binding domain
Prey - transcriptional activating domain

Come together is complementary bait and prey to allow transcription of something which allows yeast to survive

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15
Q

What NMDAR subunit binds to psd-95? And where in psd-95 does it bind?

A

GluN2B
Pdz 2

However 2A and 2B bind to pdz 1 and 2 by 2B has high affinity for pdz-2

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16
Q

What does GRIP an abbreviation for?

A

Glutamate Receptor Interacting Protein

17
Q

What does PICK1 an abbreviation for?

A

Protein Interacting with C-kinase 1

18
Q

What ionotropic glutamate receptor binds to GRIP and PICK1?

A

AMPARs

19
Q

PICK1 binds with which subunits of AMPARs?

A

GluA2 and GluA3

20
Q

What did Xi et al show in regards to PICK1 and GluA2 and 3 subunits?

A

They are colocalised via immunohistochemistry

21
Q

What is the motif on AMPARs which allows them to interact with pdz domains?

A

SVKI C terminal (on GluA2 and GluA3)

Shares homologous with xT/SxV motif

22
Q

What pdz domains of grip do AMPARs bind to?

A

Pdz 4 and 5

They also co immunoprecipitate

23
Q

What phosphorylates GluA2 subunits to regulate scaffolding binding?

A

PKC

24
Q

Where does PKC phosphorylate GluA2 subunits? What does this achieve?

A

S880
Promotes binding to PICK1 over GRIP
this is linked to internalisation and LTD

25
Q

What does TARPS stand for? give an example

A

Transmembrane AMPA receptor regulatory protein

Stargazin

26
Q

Stargazin is similar to what other protein?

A

Gamma subunit for voltage gated calcium channels

27
Q

Stargazin interacts with what ionotropic glutamate receptor?

A

AMPA

site of interaction unknown

28
Q

Functions of stargazin

A

Permits indirect associate of AMPARs with psd-95
AMPA surface delivery
Anchoring
Lateral translocation

29
Q

What type of experiments show stargazin interacts with psd-95?

A

Co-immunoprecipitation

Immunohistochemistry shows punctate fluorescent blobs when coexpressed

30
Q

What particular subunit has been studied for the role of stargazin in ampa surface delivery?

A

GluR1
Deleting the terminal 4 amino acids of stargazin reduces mEPSPs at post synaptic membrane as it cannot bind to psd-95

Therefore, although psd-95 is not important for number of AMPARs at membrane it is important for post synaptic membrane localisation

31
Q

What does mGluR receptors scaffold to?

A

Homer

32
Q

What group discovered the association of mGluR5 and Homer?

What technique was used?

A

Brakeman et al 1997

Yeast two hybrid and coimmunopreciptation with antihomer antibody then stain for mGluR5

33
Q

What domain of homer binds to mGluR?

A

EVH1 domain bind to the c terminus if mGluR

EVH1 is in someways similar to pdz and contains GLGF repeats and an upstream arginine

34
Q

What does an increase in synaptic activity do it homer

A

It increases its expression

35
Q

What are the 2 domains of homer from C-N terminus?

A

C terminus - coiled coil + leucine zipper - EVH1 - N terminus

36
Q

What is the function of the coiled coil and leucine zipper domain on homer?

A

Allows for homomeric and hetromeric interactions between homer isoforms

Molecular and Cellular Neuroscience (11 decks)

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