Membranes and receptors - 7

Question 1

What is signal transduction?

Answer 1

A basic process in molecular cell biology involving the conversion of a signal from outside the cell to a functional change within the cell.

Question 2

What are the three “superfamilies” of cell-surface receptor?

Answer 2

1. Ligand-gated (receptor-operated) ion channels e.g. nAChR
2. Receptors with intrinsic enzymatic activity (receptor tyrosine kinases e.g. insulin receptor)
3. G-protein coupled (7TM) receptors (e.g. mAChR)

Question 3

How do insulin receptors work?

Answer 3

1. Insulin binds to their alpha-subunits -> conformational change
2. Beta-subunits come closer together and auto-phosphorylate each others’ tyosine residues
3. These changes recruit adaptor molecules which then control downstream processes which control blood glucose homeostasis.

Question 4

What are agonists?

Answer 4

Ligands that bind to the receptor and activate it (leading to intracellular transduction events).

Question 5

What are antagonists?

Answer 5

Ligands that bind to the receptor but DO NOT ACTIVATE it (block the effects of agonists at the receptor).

Question 6

Names some beta-2 adrenoceptor agonists which are anti-asthma:

Answer 6

Salbutamol and salmeterol.

Question 7

Name some u-opioid receptor agonists which are used for analgesia/anaesthesia:

Answer 7

Morphone and fentanyl.

Question 8

Name some beta-adrenoceptor antagonists which are used to manage hypertension:

Answer 8

Propranolol and atenolol (b1 selective).

Question 9

Name some D2 dopamine receptor antagonists which are anti-schozophrenic:

Answer 9

Haloperidol and sulpiride.

Question 10

Gene mutation to which GPCR causes retinitis pigmentosa?

Answer 10

Loss-of-function mutation of Rhodopsin.

Question 11

Gene mutation to which GPCR causes nephrogenic diabetes insipidus?

Answer 11

Loss-of-function mutation of V2 vasopressin receptor -> polyuria.

Question 12

Gene mutation to which GPCR causes familial male preocious puberty?

Answer 12

Gain-of-function mutation to the LH receptor.

Question 13

List some stimuli that GPCRs respond to:

Answer 13

Sensory GPCRs: light, odours and tastes.

Different GPCRs: ions, neurotransmitters, peptide and non-peptide hormones, large glycoproteins.

Question 14

What type of hormone is glucagon?

Answer 14

Peptide hormone

Question 15

What type of hormone is adrenaline?

Answer 15

Catecholamine (group of monamines)

Question 16

What type of hormone is TSH?

Answer 16

Large glycoprotein

Question 17

What are the basic structural features that all GPCRs share?

Answer 17

1. Single polypeptide chain (300-1200 aa)
2. 7TM-spanning regions
3. Extra-cellular N-terminal
4. Intracellular C-terminal

Question 18

Which are the two regions of the GPCR that can be responsible for ligand binding?

Answer 18

For some receptors the ligand-binding site is:

1. Formed by 2-3 of the transmembrane domains
2. The N-terminal region (and other extracellular domains) - most likely for large ligands (but not necessarily).

Question 19

What governs receptor G-protein selection?

Answer 19

1. Activated GCPRs preferentially interact with specific types of G-protein
2. G-protein alpha- and beta/gamma-subunits interact with specific effector proteins.

Question 20

What type of G-protein is specific for the GPCR Rhodopsin? What pathway does it activate?

Answer 20

Gt-apha protein. It activates cGMP phosphodiesterase.

Question 21

What is wooping cough (pertussis)?

Answer 21

Pertussis is a highly contagious bacterial disease (caused by Bordetella pertussis) that causes uncontrollable, violent coughing - which can make it hard to breathe. A deep ‘wooping’ soudn i s often heard when the patient starts to take a breath.

Question 22

What are the effects of the cholera toxin on Gs-apha proteins What is the clinical effect of this?

Answer 22

They ADP-ribosylate this Gs-apha protein which causes irreversible activation because it interferes with its GTPase activity, therefore the signal cannot be inactivated. This causes increased levels of cAMP in the gut epithelium which in turn leads to secretion of H2O, Na+, K+, Cl−, and HCO3− into the lumen of the small intestine and rapid dehydration.

Question 23

What are the effects of the pertussis toxin on Gi-alpha proteins?

Answer 23

They ADP-ribosylate this Gi-alpha protein which causes it to be irreversibly INactivated becuases the Gi-alpha protein can no longer be activated by GPCRs.

Question 24

List some enzyme effectors activated by G-proteins:

Answer 24

1. Adenylyl cyclase: (ATP->cAMP)
2. Phospholipase C: (PIP2 -> IP3 and DAG)
3. Phosphoinositide 3-kinase (PI3K): (PIP2 -> PIP3)
4. cGMP phosphodiesterase: (cGMP -> 5’-GMP)

Question 25

List some ion channel effectors of G-proteins:

Answer 25

1. VOCC

2. G protein-regulated inwardly-rectifying K+ channels (GIRKs).

Question 26

What is the differnence in the role of GPCR and G-protein in the signalling pathway?

Answer 26

GPCR receives the extracellular signal and G-protein spreads an intracellular signal by activating/deactivating effector molecules intracellularly.