Session 6 - Receptors and membrane turnover

Question 1

Does a molecules only fall into one category of function?

Answer 1

-No it can be multiple

Question 2

In what two ways can intercellular signalling occur?

Answer 2

• Secreted molecules

- PM-bound molecules

Question 3

What is paracrine signalling?

Answer 3

-Cells secrete local chemical mediators to communicate with other local cells

Question 4

What is endocrine signalling?

Answer 4

-Hormones released into the blood stream and effect a distal target tissue

Question 5

Why do hydrophilic molecules have to act through surface receptors?

Answer 5

-Cannot cross membrane

Question 6

What is meant by a receptor being functionally silent?

Answer 6

-The receptor is in its unbound state, having no effect on the cell

Question 7

What is an agonist?

Answer 7

-A ligand which produces activation of a receptor

Question 8

What is an antagonist?

Answer 8

-A ligand which does not cause activation when it binds to the receptor and prevents an agonist binding

Question 9

What is a partial agonist?

Answer 9

-An agonist which does not generate maximum cellular response

Question 10

What is an acceptor?

Answer 10

-A receptor which operates in the absence of a ligand, however it is regulated by the ligands which do bind to it

Question 11

Which binding has a higher affinity, enzyme-substrate or receptor-ligand?

Answer 11

-Receptor-ligand

Question 12

How are receptors classified?

Answer 12

-1st based on the specific ligands they bind
-Subclassified based on the affinity of a series of agonists and antagonist they bind
eg classification -> acetylcholine receptors
Agonist -> nicotinic (nicotine agonist)/muscarinic (muscarine)
Antagonist -> M1/M2/M3 in order of affinity for antagonist

Question 13

What are super-families?

Answer 13

-A large group of receptors which all share the same basic structure

Question 14

In what 4 ways does transduction of an extracellular signal occur involving receptors?

Answer 14

1) Membrane bound receptors with integral ion channels
2) Membrane bound receptors with integral enzyme activity
3) Membrane bound receptors which couple to G-proteins
4) Intracellular receptors

Question 15

What type of receptors are membrane bound receptors with integral ion channels?

Answer 15

• Ligand-gated channels

- Voltage-gated channels

Question 16

Why are ‘classical’ ligand-gated ion channels a superfamily?

Answer 16

• They have similar pentameric structures, with each subunit having 4 TMD
• One TMD forms the pore which has 2+ve/-ve charges on it making it cation/anion selective

Question 17

Name some ‘classical’ ligand-gated ion channels

Answer 17

• NachR
• GABA R
• Glycine R
• Glutamate receptor

Question 18

Why are some ligand-gated channels ‘non-classical’?

Answer 18

-Structurally distinct from other ligand-gated ion channels

Question 19

Name some ‘non-classical’ ion channels

Answer 19

• ATP-sensitive K channel
• IP3 receptor
• Ryanodine receptor

Question 20

How do ligand-gated intergral ion channel receptors work?

Answer 20

• Ligand binds to receptor
• Conformational change
• Gated channel opens

Question 21

How does an membrane bound receptor with integral enzyme activity work?

Answer 21

• Agonist binds causing conformational change

- Activates intrinsic enzyme activity

Question 22

Give an example of a group of membrane-bound receptors with intrinsic enzymatic activity

Answer 22

-Tyrosine kinase receptors

Question 23

How do receptor tyrosine kinases work?

Answer 23

• Agonist binds causing receptor dimerisation and activation of a protein kinase in the cytoplasmic domains of the receptors
• Receptors autophosphorylates tyrosine residues on the opposite dimerised receptor
• Phosphorylated tyrosines are either recognised directly by enzymes or by transducing proteins
• The effector enzymes then become allosterically activated -> transducing the message to the intracellular environment

Question 24

What must effector enzymes have to directly recognise phosphotyrosine residues on RTK?

Answer 24

-SRC-homology-2 domains (Phosphotyrosine recognition sites)

Question 25

Give an example of a receptor tyrosine kinase

Answer 25

-Growth factor receptors (EGFR, PDGFR)

Question 26

What is a G-protein?

Answer 26

-GTP-binding regulatory proteins

Question 27

How many transmembrane domains do GPCRs have?

Answer 27

-7

Question 28

How are chemical signals classified based on function?

Answer 28

• Hormones; signalling between different tissues via the circulation
• Neurotransmitters; signalling at specialised cell junctions
• Local chemical mediators; signalling between adjacent cells in the same tissue

Question 29

What are the possible effector enzymes of GPCRs?

Answer 29

• Adenyl cyclase
• Phospholipase C
• Ion channels

Question 30

Give examples of GPCRs

Answer 30

• Muscarinic Ach
• Adrenoreceptors
• Dopamine receptors

Question 31

What type of molecules use intracelluar receptors?

Answer 31

-Hydrophobic

eg steroid hormones, thyroid hormones

Question 32

Where are the intracellular receptors in the resting state?

Answer 32

-Bound to hsp for stability in the cytoplasm

Question 33

What happens to an intracellular receptor when an agonist binds?

Answer 33

• Activated receptor dissociates from hsp/chaperone and the receptor:agonist translocates to the nucleus
• Conformational change occurs to expose DNA binding domain of receptor
• Receptor binds and regulates gene transcription

Question 34

Why does amplification of a signal produced by an extracellular ligand have to occur?

Answer 34

-The concentration of extracellular ligand binding is relatively low, so if order to produce the maximal response the signal has to be amplified

Question 35

How does amplification of a signal occur?

Answer 35

-The activation of one enzyme can modify multiple target enzymes beginning a cascade

Question 36

Give an example where agonist binding inhibits a target effector rather than activates it

Answer 36

• In cardiac pacemaker cells ach acting on M2 receptors decreases the HR
• In hepatocytes, glucagon stimulates glycogen breakdown