MnR S6 - Receptors and receptor mediated endocytosis

Question 1

List the groups of secreted chemical signalling molecules according to their function

Answer 1

Local chemical mediators, hormones, neurotransmitter

Question 2

Define receptor

Answer 2

Molecule that recognises specifically a second molecule (ligand) or family of molecules and which in response to a ligand binding brings about regulation of a cellular process

Question 3

List some roles of ligands in cellular physiology

Answer 3

• Signalling by hormones
• Neurotransmission
• Cellular delivery
• Control gene expression
• Cell adhesion
• Modulation of immune response
• Sorting intracellular proteins
• Release of intracellular calcium ion stores

Question 4

Define ligand

Answer 4

Any molecule that binds specifically to a receptor site. May be an agonist or antagonist

Question 5

How does the binding affinity for ligands at receptors compare to substrates and allosteric regulators at enzyme sites?

Answer 5

Binding affinity much higher between ligands and receptors (KD) than KM

Question 6

Outline another key difference between ligand and receptor binding and enzyme and substrate binding

Answer 6

Substrate molecule is chemically modified by a chemical reaction catalysed by the active site whereas ligand bound to a receptor site is not altered

Question 7

How do acceptors differ from receptors?

Answer 7

Operate normally in the absence of ligand and ligand binding alone produces no response

Question 8

List the four methods of signal transduction

Answer 8

• Membrane-bound receptor with integral ion channel
• Membrane-bound receptor with integral enzyme activity
• Membrane-bound receptor which couples to effectors via transducing proteins
• Intracellular receptors

Question 9

How can receptors be classified?

Answer 9

• According to the specific physiological signalling molecule recognised
• Sub-classified by affinity of antagonists

Question 10

Describe the structure of the nAChR and the ions it allows in

Answer 10

• Five sub-unit made up of 4 transmembranous domains each

- K+, Na+ and Ca2+

Question 11

How does the structure of the nAChR ensure that only cations move through?

Answer 11

Contains charge residues

Question 12

Give example of other membrane-bound receptors with integral ion channels

Answer 12

• GABA receptor
• Glycine receptor
• Glutamate receptor

Question 13

Which enzyme are growth factor receptors: EDF, PDGF and insulin linked to?

Answer 13

Tyrosine kinase

Question 14

How do tyrosine kinase linked receptors work?

Answer 14

• Ligand binds stimulating auto-phosphorylation of the cytoplasmic side of the receptor
• An enzyme OR a transducer then recognises the phosphotyrosine which activates the phosphorylation pathway

Question 15

What is another name for membrane-bound receptors which couple to effectors via transducing proteins?

Answer 15

7TMD receptors which are coupled through G-proteins enzymes of channels

Question 16

Where is the binding domain located on 7TMD receptors?

Answer 16

Normally within the plane of the bilayer or sometimes at N-terminus

Question 17

Where is the G-protein coupling domain located?

Answer 17

Cytoplasmic side of membrane near the C-terminus

Question 18

Outline how adrenaline binding to beta-adrenoceptors is transduced into the cell

Answer 18

• Adrenaline binds
• GDP bound to third sub-unit (alpha) is released
• GTP binds to the alpha sub-unit
• The three sub-units dissociate
• Alpha subunit goes on to activate adenylyl cyclase

Question 19

How are intracellular receptors kept silent at rest?

Answer 19

Inhibitory protein complex blocks DNA binding domain and is released when steroid hormone binds

Question 20

What is phagocytosis and by what mechanism does it occur?

Answer 20

Internalisation of particulate by the zippering mechanism

Question 21

What is pinocytosis and what is its function?

Answer 21

Invagination of the plasma membrane to form a vesicle, enabling the uptake of extracellular solutes

Question 22

What is endocytosis?

Answer 22

Selective internalisation of molecules into the cell by binding of specific cell surface receptors

Question 23

What is the clathrin coat and how it is formed?

Answer 23

Coated pits form spontaneously from clathrin triskelions, made up of hexagons and pentagons forming three light and three heavy chains

Question 24

How is the clathrin coat removed?

Answer 24

Vesicles are uncoated in an ATP-dependent reaction

Question 25

List two coat proteins other than clathrin and where they would be found

Answer 25

• COP I - endoplasmic reticulum

- COP II - golgi

Question 26

By which two mechanisms can mutations in LDL receptors result in hypercholesterolemia?

Answer 26

Non functional receptor - No LDL binding, normal coated pits and internalisation

Receptor binding normal - no internalisation, LDL receptors widely distributed on cell surface, deletion of c-terminal cytoplasmic domain prevents interaction with clathrin coat

Question 27

What causes the dissociation between LDL receptors and LDL?

Answer 27

Low pH in the endosome/compartment of uncoupling receptor and ligand (CURL) caused by the H+-ATPase which pumps protons into the endosome

Question 28

What is the fate of the ligand and receptor in LDL uptake?

Answer 28

Ligand - degraded

Receptor - recycled

Question 29

Outline process of Fe3+ uptake by transferrin

Answer 29

• Ferrotransferrin bind to transferrin receptors
• Uptake into cell
• pH in vesicle decreased due to H+-ATPase
• Fe3+ released into cytosol
• Apotransferrin and receptor are recycled to the cell surface
• Neutral pH of surface compared to the endosome causes dissociation of receptor
• Both receptor and ligand recycled

Question 30

In insulin uptake, what is the fate of the ligand and receptor?

Answer 30

Ligand and receptor are both degraded

Question 31

What is the fate of the ligand and receptor in immunoglobulin uptake?

Answer 31

Both transported

Question 32

How does entry of membrane-enveloped virus into cells take advantage of receptor mediated endocytosis?

Answer 32

• By binding to cells by fortuitous association with cell receptors
• Enters cells via clathrin-coated pits
• By unfolding hydrophobic domains in membrane fusion proteins due to the acidic pH of the endosome
• By inserting membrane fusion proteins into the endosome membrane causing membrane fusion and release of genomic RNA into cell cytoplasm

Question 33

What do cholera and diphtheria toxins bind to?

Answer 33

GM1 ganglioside