L4 - receptors

Question 1

list the (3) locations receptors can be located, and give examples for each

Answer 1

plasma membrane
-LGIC, GPCR, intrinsic enzymes

Intracellular receptors (on organnelle membranes, eg mitochondria or vesicles)

• Ryanodine receptors
• VMAT
• IP3

Nuclear receptors (which interact with DNA)
- Steroid receptors

Question 2

list the 4 functional types of receptors

Answer 2

LGIC
GPCR
intrinsic enzymes
Nuclear receptors

Question 3

briefly desrcibe the basic fucntion of Ryanodine and IP3 receptors

Answer 3

LGIC that allow Ca2+ entry

Question 4

give examples of nuclear receptors (DNA binding receptors)

Answer 4

oestrogen receptor
retinoic acid receptor
steroid receptors

Question 5

describe structure of Nuclear receptors

Answer 5

LBS on the C terminal
dimerisation domain on the N terminus

between the dimerisation domain and the LBS there are zinc fingers

Question 6

what is the importance of the dimerisation domain on nuclear receptors

Answer 6

receptors exist as monomers but dimerise with another ligand-bound receptor to become activated before entering the nucleus

Question 7

describe the mechanism of nuclear receptor activation

Answer 7

1. ligand binding to receptor activates it, but it must dimerise with another activated receptor before it can enter the nucleus
2. after dimerisation the receptor can cross into nucleus and can alter expression of genes
3. alters mRNA expression and so alters protein synthesis

Question 8

where are intracellular membrane receptors found in neurones?

Answer 8

ER memrbane

Question 9

describe ryanodine receptor

Answer 9

ligand gated calcium channel -> activated by Ca2+ (and some other ligands)

causes Ca2+ release from ER or SR (Ca2+ activated calcium release)

Question 10

describe IP3 receptor

Answer 10

ligand gated Ca2+ channel - activated by 2nd messenger inositol 1,4,5 triphosphate (IP3)

causes Ca2+ release form ER or SR

Question 11

where are IP3 and ryanodine receptors located?

Answer 11

membranes of SR or ER

Question 12

list the types of plasma membrane receptors

Answer 12

LGIC
GPCR
intrinsic enzyme receptors

Question 13

what are the 3 main types of LGIC families

Answer 13

Nicotinic receptor like
ATP receptors (P2X)
Ionotropic glutamate receptors

Question 14

gove examples of Nicotinic R like ion channels

Answer 14

NAChR
5-HT3
GABA(A)
Glycine 
ZAC (zinc activated)

Question 15

how many types of P2x receptor are there

Answer 15

7

Question 16

what is the difference between ATP P2x and P2Y receptors?

Answer 16

P2X -> the LGIC ATP receptors

P2Y -> the GPCR ATP receptors

Question 17

what are the types of LGIC glutamate receptors

Answer 17

NMDA
AMPA
Kainate

Question 18

descirbe structure of N R like receptors
subunits 
TMD
N&C terminal 
LBS 
pore?

Answer 18

5 subunits
4 TMDs
extracellular N and C terminal 
N terminal LBS
TMD2 is pore

Question 19

descirbe structure of ATP receptors
subunits 
TMD
N&C terminal 
LBS 
pore?

Answer 19

3 subunits 
2 TMDs 
intracellular N & C temrinal
LBS on extracellular loop between the 2 TMDs
pore in TMD2

Question 20

descirbe structure of ionotropic glutamate receptors
subunits 
TMD
N&C terminal 
LBS 
pore?

Answer 20

4 subunits
3 TMDs
extracellular N terminal 
intracellular C terminal
LBS on large loop of N terminal
inverted P loop between TMDs 1&2 which form the pore

Question 21

what are the LGICs permeable to?

Answer 21

inhibitory ones (GABA & Glycine) -> Cl-

excitatory ones (most others) -> Na / Ca2+ in and sometimes K+ out

Question 22

what aspect of the pore determines what ions can pass through?

Answer 22

the AA sequence and presence of ions (charge)

Question 23

list the main 3 GPCR subfamilies (and give examples for each)

Answer 23

• Rhodopsin like (mACH, opioid, P2Y, all serotonin except 5-HT3)
• metabotropic Glutamate receptor like ( GABA(B), mGluRs)
• secretin receptor like (VIP, parathyroid hormone)

Question 24

describe structure of Rhodopsin like GPCRs

Answer 24

• 7 TMDs
• extracellular N
• intracellular C
• G protein coupling region loop between TMD 5&6
• LBS small molecules (in TMDs)
• LBS larger molecules on extracellular N terminal

Question 25

what structure are all TMDs

Answer 25

a helices

Question 26

describe structure of metabotrophic glutamate like receptor

Answer 26

``` 7 TMDs extracellular large looping N terminal intracellular C terminal G protein coupling region loop on TMD 2&3 LBS on large N terminal loop ``` found as dimers the LBS will be found on one monomer and the G protein coupling region on the other

Question 27

briefly describe GPCR function mechanism

Answer 27

1. ligand will bind, activating receptor causing it to interact with G protein 2. GDP converted to GTP causing G protein to dissociate (a and By) 3. a subunit will diffuse and interact with enzymes in cytosol etc By subunit can diffuse along membrane and act on ion channels

Question 28

why does the By subunit of a g protein remain near membrane?

Answer 28

lipidation of AAs in By subunit cause it to stay close to membrane

Question 29

list the two main types of intrinsic enzyme receptor families (and give examples)

Answer 29

receptor tyrosine kinases (insulin receptor) | receptor guanylyl cyclase (atrial natruiretic peptide)

Question 30

what are intrinsic enzyme receptors

Answer 30

receptors that when activated act like enzymes

Question 31

describe mechanism of intrinsic enzyme receptor activation

Answer 31

1. ligand binding 2. two ligand-bound receptors dimerise 3. autophosphorylation - receptors phosphorylate eachother causing conformational change exposing the catalytic site of the receptors 4. other substrates can then bind and be phosphorylates

Question 32

describe process of receptor synthesis

Answer 32

1. DNA -> RNA in nucleus 2. RNA -> mRNA in rough ER 3. mRNA -> protein in smooth ER (where N glycosylation occurs) 4. protein O glycosylation occurs in Golgi 5. protein sorted by sort system `

Question 33

describe process of receptor sorting and trafficking

Answer 33

1. all proteins have 'sort sequence' which allows their sorting by a sort system 2. receptors are co transported with vesicles going to the same location, to where they need to be (along with their G protein if they are a GPCR) 3. if the receptor is no longer needed or is damaged, it will travel back to where it originated from (this wont be coupled to the G protein if its a GPCR)

Question 34

how do rhodopsin like GPCRs and mGluRs differ?

Answer 34

rhodopsin has short N terminal mGluR has long N terminal mGluR receptors often have to dimerise to become functional their ligand binding is different