Lecture 6 - Receptors and Membrane Turnover

Question 1

what is a receptor?

Answer 1

a molecule that recognises specifically a second molecule or family of molecules - in response to binding, brings about regulation of a cellular process

Question 2

what is a ligand?

Answer 2

a molecule that binds specifically to a receptor site

Question 3

what is an agonist?

Answer 3

ligand that produces the activation of a receptor

Question 4

what is an antagonist?

Answer 4

ligand that binds without causing activation

Question 5

when is signal transduction needed?

Answer 5

hydrophilic signalling molecules can’t pass through the cell membrane to produce a response inside the cell

Question 6

how do membrane bound receptors achieve signal transduction?

Answer 6

integral ion channels
integral enzyme activity
coupling to effectors through transducing proteins

Question 7

what happens with membrane bound receptors with integral ion channels?

Answer 7

agonist binding to ligand gated ion channels results in a conformational change and the opening of a gated channel to permit ion flow down an electrochemical gradient

Question 8

what happens with membrane bound receptors with integral enzyme activity?

Answer 8

agonist binding to the extracellular domain of receptors causes a conformational change which activates intrinsic enzyme activity contained within the protein structure of the receptor

Question 9

what do tyrosine kinase linked receptors do?

Answer 9

autophosphorylate on binding
phosphorylated receptor tyrosine residues are recognised by transducing proteins or enzymes containing phosphotyrosine recognition protein message is transduced into an intracellular chemical event

Question 10

what happens with membrane bound receptors with transducing proteins?

Answer 10

seven transmembrane domain receptors (7tmdr) couple to effector molecules via a transducing molecule - a g protein - therefore gpcr

Question 11

how does amplification in cell signalling work?

Answer 11

the concentration of a lot of extracellular signalling molecules is low, so there are mechanisms to increase the concentrations

Question 12

what is phagocytosis?

Answer 12

in response to the binding of a particle to receptors in the plasma membrane, the cell extends pseudopods that permit further receptor interactions leading to particle internalisation via a membrane zippering mechanism

Question 13

what is pinocytosis?

Answer 13

the invagination of the plasma membrane to form a lipid vesicle permitting the uptake of impermeable extracellular solutes and retrieval of plasma membrane

Question 14

what is receptor mediated endocytosis?

Answer 14

specific binding of molecules to cell surface receptors permits selective uptake of substances into the cell

Question 15

how is cholesterol taken up?

Answer 15

receptor mediated endocytosis

Question 16

what are ldl?

Answer 16

originate in liver
core of cholesterol molecules esterified to fatty acid
surrounded by lipid mono layer including apo b

Question 17

what happens when ldl bind to their receptors?

Answer 17

1. pit invaginates to form coated vesicles
2. vesicles are uncoated using atp
3. vesicles fuse with larger smooth vesicles called endosomes
4. pH of endosome is lower than pH of cytoplasm
5. at this pH, ldl receptor has low affinity for ldl so they dissociate - the endosome is known as curl (compartment for uncoupling of receptor and ligand)
6. receptors are sequestered to a domain within the endosome membrane which buds off as a vesicle to recycle the receptor
7. the endosome containing the ldl fuse with lysosomes where the cholesterol is hydrolysed and released into the cell

Question 18

what mutations affect the ldl receptor in hypercholesterolaemia?

Answer 18

non functioning receptor - prevents binding and uptake of ldl
receptor binding normal - deletion of c terminal cytoplasmic domain preventing interaction between receptor and clathrin coat so receptors are spread evenly rather that concentrated
receptor deficiency - mutation prevents expression of ldl receptor

Question 19

describe the uptake of Fe3+ by transferrin

Answer 19

receptor mediated endocytosis

1. two Fe3+ find to apotransferrin to form transferrin in circulation
2. transferrin binds to transferrin receptor at neutral pH and is internalised
3. reaches the acidic endosome where Fe3+ ions are released from transferrin
4. at this pH, apotransferrin is still associated with the transferrin receptor
5. complex is sorted in curl to recycle it - here at pH 7.4 the apotransferrin dissociates

Question 20

describe the uptake of occupied insulin receptors

Answer 20

1. insulin receptors congregate over clathrin coated pits once the insulin is bound
2. in the endosome insulin remains bound to the receptor and the complex goes to the lysosomes to be degraded
3. this mechanism means that the cell can be desensitised to continued high circulating insulin

Question 21

what is transcytosis?

Answer 21

ligands that remain bound to their receptors can be transported across the cell

Question 22

describe mode 1 of the pathway from coated pits to endosome

Answer 22

fate of receptor: recycled
fate of ligand: degraded
example: ldl
function: metabolite uptake

Question 23

describe mode 2 of the pathway from coated pits to endosome

Answer 23

fate of receptor: recycled
fate of ligand: recycled
example: transferrin
function: metabolite uptake

Question 24

describe mode 3 of the pathway from coated pits to endosome

Answer 24

fate of receptor: degraded
fate of ligand: degraded
example: insulin, epidermal gf; immune complexes
function: receptor down regulation; removal of foreign antigen from circulation

Question 25

describe mode 4 of the pathway from coated pits to endosome

Answer 25

fate of receptor: transported
fate of ligand: transported
examples: maternal IgG; IgA
function: transfer of large molecules across cell; eg maternal immunity to foetus via placenta or circulation to bile

Question 26

how do membrane enveloped viruses and toxins use rme?

Answer 26

1. bind to receptors in the plasma membrane
2. once in the endosome the acidic pH allows the viral membrane to fuse with the endosomal membrane
3. viral RNA is released into the cell and can be translated and replicated by the host cells machinery