Receptors and signal transduction III

Question 1

Which glutamate receptors are constitutive dimers?

Answer 1

mGluRs

Question 2

Meaning of constitutive dimers?

Answer 2

Need two for a functional receptor

Question 3

What type of dimer do mGluRs usually form?

Answer 3

Homodimers, although 16 heterodimers are possible

Question 4

Issue with homomeric mGluRs?

Answer 4

Difficult to shot they exist in the wild type brain, tho can make then in expression systems

Question 5

How can mGluRs switch between diff effectors?

Answer 5

Via interaction with scaffolding proteins

Question 6

Example of a scaffolding protein that mGluRs use?

Answer 6

Homer–>Sits postsynaptically and can direct signalling in diff ways

Question 7

Agonist biased signalling?

Answer 7

Binding of a ligand to a receptor can signal in diff ways depending on the agonist being used
Agonist can bind and direct signalling down one specific path instead of another

Question 8

Where on mGluRs does glutamate bind?

Answer 8

Venus flytrap domains (VFDs)

Question 9

VFD location and activation?

Answer 9

Two on a dimer, and activtion can occur via binding to one

Question 10

Ionotropic (NMDA, AMPA, KAINATE) glutamate receptor subunit structure?

Answer 10

3 transmembrane domain, MR re-entrant loop

Question 11

Role of re-entrant loop in an ionotropic glutamate receptor?

Answer 11

Gives rise to the pore domain of the assembled receptor

Question 12

Which receptor is an obligate heterotetromer?

Answer 12

NMDA

Question 13

Obligate heterotetramer meaning?

Answer 13

Must have diff subunits

Question 14

Which subunits do NMDA receptor always have?

Answer 14

2 GluN1

Question 15

Where does NMDA receptor diversity come from?

Answer 15

The two non-GluN1 subunits

Question 16

Role of GluN1?

Answer 16

Binding site for glycine

Question 17

What is necessary for NMDA receptor activation (as well as glutamate)?

Answer 17

Glycine

Question 18

Where on an NMDA receptor does glutamate bind?

Answer 18

GluN2/GluN3

Question 19

What are coincidence receptors?

Answer 19

Receptors that require the binding of two ligands to activate

Question 20

Example of a coincidence receptor?

Answer 20

NMDA

Question 21

What is in the middle of the channel at resting membrane potential?

Answer 21

Mg2+ ion

Question 22

What is needed for calcium or sodium to be allowed to flow through the NMDA channel?

Answer 22

Glutamate binding, glycine binding, depolarisation of the membrane (to remove Mg2+)

Question 23

NMDA regulatory sites?

Answer 23

Metal ions, redox regulation, polyamines

Question 24

What is memantine used to treat?

Answer 24

Moderate to severe AZ

Question 25

Ionotropic glutamate receptor order?

Answer 25

AMPA first, provided depolarisation to move Mg2+ from NMDA, so then NMDA opens

Question 26

Two receptor groups for ACh?

Answer 26

GPCRs and ligand gated ion channels

Question 27

ACh GPCR?

Answer 27

Muscarinic receptor

Question 28

What are muscarinic receptors sensitive to?

Answer 28

toxins from plants--> toadstool has muscarine

Question 29

Which muscarinic receptor subtypes are associated with increases in synaptic activity?

Answer 29

M1, 3, 5

Question 30

Which muscarinic receptor subtypes are associated with decreases in synaptic activity?

Answer 30

M2, M4