Session 6

Question 0

What is a receptor?

Answer 0

A molecule that recognises specifically a second molecule (ligand) or family of molecules and brings about regulation of a cellular process in response to it.

Question 1

What is a ligand?

Answer 1

A molecule that binds to a receptor site. If it causes activation it’s an agonist and if it blocks it then it’s an antagonist. Agonists which stimulate a receptor but are unable to elicit the maximum cell response possible are termed partial agonists.

Question 2

What is an acceptor?

Answer 2

A molecule whose activity is modified by the binding of small chemicals, including drugs. Their basic function can, however, be carried out without the interaction of a ligand. For example, the enzyme dihydrofolate reductase is inhibited by the binding of the drug, methotrexate.

Question 3

How do receptors and acceptors differ?

Answer 3

Receptors - silent at rest, stimulated by agonist binding

Acceptors - operate in absence of ligand, ligand binding alone has no response

Question 4

What are the four types of signal transduction?

Answer 4

Membrane-bound receptors with integral ion channels
Membrane-bound receptors with integral enzyme activity
Membrane-bound receptors with integral ions which couple to effectors through transducing proteins
Intracellular receptors

Question 5

Give some examples of membrane bound receptors with integral ion channels

Answer 5

Nicotinic acetylcholine receptors (nAChR) - gated Na+, K+ and Ca2+ channels
Gamma amino butyric acid (GABA) receptors - gated Cl- channel
Glycine receptor - gated chloride channel
Inositol 1,45-triphosphate (IP3) receptor - gated release of Ca2+ from ER

Question 6

What is the classical structure of nicotinic receptors?

Answer 6

Pentameric

Question 7

Give some examples of membrane bound receptors with integral ion enzyme activity

Answer 7

Atrial natriuretic peptide receptor (ANP) - linked directly to guanylyl cyclase (GTP –> cAMP)

Question 8

Give an example of a membrane bound receptors with integral ion which couple to effectors through transducing proteins

Answer 8

Coupled through GTP binding regulatory proteins to enzymes/channels e.g. adrenaline binding to beta adrenoreceptors activates adenylyl cyclase via Gs

Question 9

Give an example of an intracellular receptor

Answer 9

DNA binding domain (zinc fingers)

Question 10

What similarities are there between receptor binding and enzyme binding?

Answer 10

Specificity is needed, specificity of binding confers specificity to regulation of processes, generally reversible, both induce conformational changes and a change in activity of the molecule, no chemical modification of receptor binding sites or enzyme regulatory sites

Question 11

What differences are there between receptor binding and enzyme binding?

Answer 11

Affinity of ligands is generally greater, ligand isn’t chemically changed but substrate is

Question 12

What is cellular recycling?

Answer 12

Membrane is trafficked from ER to the plasma membrane via exocytotic, secretory pathway. This is done by endocytosis.

Question 13

What is vesicular transport?

Answer 13

Membrane is trafficked between organelles and between organelles and plasma membrane by membrane vesicles. Vesicles bud from the donor organelle, are trafficked to their destination, where they fuse with the recipient organelle.

Question 14

Define phagocytosis

Answer 14

Internalisation of particulate matter. Receptors recognise it and ‘zipper’ up around the particle –> fusion to lysosomes

Question 15

Define pinocytosis

Answer 15

Invagination of plasma membrane to form a vesicle. Permits uptake of extracellular solutes

Question 16

Define endocytosis

Answer 16

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

Question 17

How is cholesterol taken up by cells?

Answer 17

Receptor mediated endocytosis

Question 18

What are LDLs made up of?

Answer 18

Core of esterified cholesterol esters
Covered by a phospholipid and cholesterol monolayer
Contain apoprotein B

Question 19

What is a triskelion?

Answer 19

Coat structures made up of hexagons and pentagons formed from clathrin triskelions.
Triskelions comprise of three clathrin heavy chains and three light chains

Question 20

How do clathrin coats assemble and dissemble?

Answer 20

Coated pits form spontaneously. Clathrin coated vesicles are uncoated by an ATP-dependent uncoating protein. Clathrin triskelions are recycled to form new clathrin coated pits.

Question 21

What does CURL stand for?

Answer 21

Compartment of uncoupling of receptor and ligand

Question 22

How do cells take up LDLs?

Answer 22

Cells that require cholesterol synthesize cell surface receptors (LDL- receptor) that recognise specifically apoprotein B. Within 10 minutes of binding, the LDL particle is internalised and delivered to the lysosomes where the cholesterol is released from the cholesterol esters.

Question 23

Describe what happens when LDL’s bind to receptors

Answer 23

Coated pits invaginate and pinch off from the plasma membrane to form coated vesicles. Coated vesicles are uncoated,they then fuse with larger smooth vesicles (endosomes). The pH of the endosome ~5.5-6.0 (maintained by an ATP-dependent proton pump). At this pH the LDL-receptor has low affinity for the LDL particle and the two dissociate. The endosome is = CURL. The transmembranous receptors are sequestered to a domain within the endosome membrane which buds off as a vesicle and recycles the LDL- receptor to the plasma membrane. The endosomes containing the LDL fuse with lysosomes such that the cholesterol can be hydrolysed from the esters and released into the cell.

Question 24

Describe the three mutations that can lead to hypercholesterolaemia

Answer 24

1. Receptor deficiency - mutations prevent expression of LDL receptor. 2. Non-functional receptor - no binding of LDL, normal coated pits and internalization. 3. Receptor binding normal - no internalization due to a deletion in the C-terminal of the receptor that makes the interaction with the coated pits. LDL-receptors are found distributed over the whole cell surface in these patients.

Question 25

Describe the uptake of ferric (Fe3+) ions by transferrin.

Answer 25

Two Fe3+ ions bind to apotransferrin forming transferrin in the circulation. Transferrin, binds to the transferrin receptor at neutral pH and is internalised. On reaching the acidic endosome, the Fe3+ ions are released from the transferrin, at this pH the apotransferrin remains associated with the transferrin receptor. The complex is sorted in the CURL for recycling back to the plasma membrane, where at pH 7.4, the apotransferrin dissociates from the transferrin receptor again.

Question 26

Give examples of transcytosis

Answer 26

Maternal immunoglobulins to the foetus via the placenta, transfer of immunoglobulin A (IgA) from the circulation to bile in the liver. During transport of IgA the receptor is cleaved, resulting in the release of immunoglobulin with a bound ’secretory component’ derived from the receptor.

Question 27

Define transcytosis?

Answer 27

Transcytosis is the process by which various macromolecules are transported across the interior of a cell. Macromolecules are captured in vesicles on one side of the cell, drawn across the cell, and ejected on the other side.

Question 28

How do membrane enveloped viruses take advantage of endocytosis?

Answer 28

Bind to cells by fortuitous association with cell receptors. Enter cells via clathrin coated pits (RME). Unfolding hydrophobic domains in membrane fusion proteins in response to the acidic pH of the endosome. Insertion of membrane fusion proteins into endosome membrane, release of genomic RNA into the cell cytoplasm. Uses host cell machinery to replicate RNA & capsid proteins to bud new viruses at cell membrane