Lecture 6 - Receptors and Membrane Turnover Flashcards Preview

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Flashcards in Lecture 6 - Receptors and Membrane Turnover Deck (26)
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1
Q

what is a receptor?

A

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

2
Q

what is a ligand?

A

a molecule that binds specifically to a receptor site

3
Q

what is an agonist?

A

ligand that produces the activation of a receptor

4
Q

what is an antagonist?

A

ligand that binds without causing activation

5
Q

when is signal transduction needed?

A

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

6
Q

how do membrane bound receptors achieve signal transduction?

A

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

7
Q

what happens with membrane bound receptors with integral ion channels?

A

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

8
Q

what happens with membrane bound receptors with integral enzyme activity?

A

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

9
Q

what do tyrosine kinase linked receptors do?

A

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

10
Q

what happens with membrane bound receptors with transducing proteins?

A

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

11
Q

how does amplification in cell signalling work?

A

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

12
Q

what is phagocytosis?

A

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

13
Q

what is pinocytosis?

A

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

14
Q

what is receptor mediated endocytosis?

A

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

15
Q

how is cholesterol taken up?

A

receptor mediated endocytosis

16
Q

what are ldl?

A

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

17
Q

what happens when ldl bind to their receptors?

A
  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
18
Q

what mutations affect the ldl receptor in hypercholesterolaemia?

A

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

19
Q

describe the uptake of Fe3+ by transferrin

A

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
20
Q

describe the uptake of occupied insulin receptors

A
  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
21
Q

what is transcytosis?

A

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

22
Q

describe mode 1 of the pathway from coated pits to endosome

A

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

23
Q

describe mode 2 of the pathway from coated pits to endosome

A

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

24
Q

describe mode 3 of the pathway from coated pits to endosome

A

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

25
Q

describe mode 4 of the pathway from coated pits to endosome

A

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

26
Q

how do membrane enveloped viruses and toxins use rme?

A
  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