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ESA 2 SK > MR 6 Receptors and Membrane Turnover > Flashcards

MR 6 Receptors and Membrane Turnover Flashcards

1
Q

What is a receptor?

A

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

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2
Q

How are receptors classified?

A

Primarily by specificity to a physiological signalling molecule then subdiveded based on affinity to a series of antagonists

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3
Q

How does the affinity of ligands at receptor sites compare with enzyme and substrate affinity?

A

Much higher with receptors and ligands as ligands may be present only in very small concentrations

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4
Q

What is an acceptor?

A

Often mistakenly called a receptor, these operate in the absence of their ligand and upon ligand binding often cease to operate. RECEPTORS MUST BE SILENT AT REST

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5
Q

What is a ligand?

A

Any molecule that binds specifically to a receptor site

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6
Q

What is an agonist?

A

Ligand producing activation of a receptor

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7
Q

What is an antagonist?

A

Ligand that binds without activating receptor, blocking receptor

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8
Q

What kind of signalling molecules require signal transduction?

A

Hydrophilic as unlike hydrophobic molecules they cannot cross the cell membrane and bind to receptors inside the cell so they bind to extracellular receptors at the cell surface which transmit the signal into the cell

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9
Q

What type of signalling molecules often have carrier proteins carrying them through the blood?

A

Hydrophobic

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10
Q

In what ways do membrane bound receptors achieve signal transduction?

A

Integral ion channels
Integral enzyme activity
Coupling to effectors via transducing proteins

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11
Q

Give an example of a receptor in the classical ligand gated ion channel family and the general structure these share.

A

Nicotinic Ach receptors

Pentameric sub unit structure with 4 transmembrane domains

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12
Q

What is paracrine signalling?

A

Signalling molecule is a local mediator which diffuses through cells and binds to receptors

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13
Q

Give some examples of roles of receptors

A 
Signalling via hormones and chem mediators
Neurotransmission
Cellular delivery
Control of gene expression
Cell adhesion
Modulation of immune response
Sorting intracellular proteins
Release of intracellular calcium stores
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14
Q

Give some examples of receptors with integral ion channels

A 
nAchr (gated Na+, K+, Ca2+ channel)
GABA receptor (gated Cl- channel)
Glycine receptor (gated Cl- channel)
Glutamate receptors
IP3 receptor (gated release of Ca2+ from ER
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15
Q

Give an example of a non-classical receptor with integral ion channel

A

Ryanodine receptor (Ca2+)

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16
Q

How do MBRs with integral enzyme activity work?

A

Agonist binding to extracellular domain causes a conformational change which activates an intrinsic enzyme contained within the protein structure of the receptor e.g tyrosine kinase

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17
Q

How do tyrosine kinase linked receptors work?

A

Autophosphorylate upon ligand binding
Phosphorylates receptor tyrosine residues are recognised by transducing proteins or directly by enzymes containing phosphotyrosine recognition sites.
Effector enzymes become activated allosterically/ by tyrosine phosphorylation by the receptor kinase.
This transduces the message int oan intracellular chemical event

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18
Q

Give an example of a tyrosine kinase linked receptor

A

Insulin receptor

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19
Q

What type of MBRs have transducing proteins?

A

7TMDRs

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20
Q

What is a G protein?

A

GTP-binding regulatory protein

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21
Q

Give examples of 7TMRs

A

mAchRs, dopamine receptors

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22
Q

Are there often more than one G protein receptor for an agonist or is it usually one?

A

Often multiple e.g M1-5 mAchRs

23
Q

What is integrated signalling?

A

When separate g-protein receptors act simultaneously to both simultaneously to both stimulate and inhibit the effector to produce a measured effect

24
Q

What are intracellular receptors bound to in their resting state?

A

Heat shock or chaperone proteins

25
What happens when a ligand binds to an intracellular receptor?
Activated receptor dissociates from the stabilising protein and translocates to the nucleus where it binds to control regions in DNA, regulating gene expression
26
Which act slower, intracellular or extracellular receptors?
Intracellular as dependant on transcription and translation
27
Explain amplification in cellular signalling
Often the conc of extracellular signalling molecules is very low. The binding of a signal molecule to one receptor can cause the modification of thousands of substrate due to activating an enzyme. Enzymatic cascades can produce further amplification
28
What signalling molecule binds to what receptors in cardiac pacemaker cells to increase heart rate?
Noradrenaline to b1 adrenoreceptors
29
What signalling molecule binds to what receptor in cardiac pacemaker cells to reduce heart rate?
Acetylcholine to M2 muscarinic receptors
30
Where is phagocytosis found in mammals?
Specialised cells- macrophages and neutrophils
31
What happens when particles bind to receptors in the plasma membrane of phagocytes?
The cell extends pseudopods that permit further receptor interactions and particle internalisation via a 'membrane zippering' mechanism
32
What happens to internalised phagosomes?
Fuse with lysosomes to form phagolysosomes in which the particulate material is degraded
33
How is cell membrane recycled?
Membrane trafficked from ER via exocytosis | As membranes don't become ruffled must be an opposite movement of cell membrane back into cell via endocytosis
34
What is uptake of cholesterol an example of?
Receptor-Mediated Endocytosis
35
What is pinocytosis?
The invagination of plasma membrane to form a lipid vesicle to permit the uptake of impermeable extracellular solutes and retrieval of plasma membrane. Can be subdivided into two forms: fluid phase and receptor mediated endocytosis
36
What is Receptor Mediated Endocytosis?
When specific binding of molecules to cell surface receptors permits selective uptake of substances into the cell
37
Where do LDLs originate and what is their structure?
Originate in liver Cholesterol esterified to fatty acid core surrounded by lipid monolayer containing phospholipid, cholesterol and single protein species, apoprotein B
38
Where are the LDL receptors that recognise apoprotein B located?
In clusters over clathrate coated pits that cover about 2% of cell's surface. These pits form spontaneously just as clathrin spontaneously forms cages
39
What happens when LDL binds to their receptors?
The clathrin pit invaginates to form a coated vesicle
40
What happens to the coated vesicles?
They are uncoated in a process that requires ATP (as forms spontaneously) and fuse with endosomes
41
What is an endosome and what's the pH?
Large smooth vesicle with pH lower than cytoplasm 5.5-6.0
42
What happens in the endosome?
The lower pH causes lowered affinity of LDL receptor for LDL so the two dissociate.
43
What is the endosome also known as and why?
Compartment for Uncoupling of Receptor and Ligand (CURL) because this is where receptor and ligand uncouple.
44
What happens to the LDL receptors after uncoupling?
Sequestered to a domain within endosome membrane which buds off as vesicle and recycles LDL receptor to plasma membrane
45
What happens to the endosome containing LDL?
They fuse with lysosomes and cholesterol is hydrolysed from esters and released into cell
46
What mutations can affect the LDL receptor in hypercholesterolaemia?
Non-functioning receptor- mutation to LDL binding site Receptor binding normal-deletion of C terminal cytoplasmic domain preventing interaction between receptor and clathrin coat meaning receptors over entire cell surface instead of being concentrated in the 2% Receptor deficiency- mutation caused by mutation preventing LDL receptor expression
47
Describe Fe3+ ion uptake by transferrin as an example of RME
Two Fe3+ bind to apoptransferrin to form transferrin in circulation Transferrin binds to transferrin receptor at at neutral pH and internalised in similar way to cholesterol In acidic endosome Fe3+ ions released but apoptransferrin remains bound to transferrin receptor which is recycled back to plasma membrane where at pH 7.4 the apoptransferrin dissociates
48
Describe uptake of occupied insulin receptors
Unlike cholesterol and iron, insulin receptors only congregate over clathrin coated pits when agonist bound Insulin binding induces conformational change in receptor allowing it to be recognised by pit In endosome insulin stays bound to receptor and complex targeted to lysosomes for degradation This mechanism allows for reduction of receptors on membrane surface desensitising cell to continued high insulin conc
49
Explain transcytosis
Some ligands that remain bound to receptor are transported across cell e.g transfer of immunoglobulin A (IgA) from circulation to bile in liver. During transport of IgA receptor is cleaved giving IgA with bound secretory component derived from receptor
50
What is common in the 4 modes of RME?
Receptors enter via the same clathrin coated pits and pathway to endosome is the same
51
On what basis are the different modes of RME determined?
Destination of internalised receptor and ligand
52
What are the 4 modes of RME?
1- receptor recycled- ligand degraded- metabolite uptake e.g LDL 2- receptor recycled- ligand recycled- metabolite uptake e.g transferrin 3- receptor degraded- ligand degraded- receptor down reg e.g insulin, EGF. Removal of foreign antigens by immune complexes 4- receptor transported- ligand transported- transfer of large molecules across cell e.g IgA and maternal IgG giving fetal immunity
53
How does RME contribute to type 2 diabetes?
Desensitises cell to insulin when it's high for extended periods in circulation
54
How do membrane enveloped viruses and toxins take advantage of RME to enter cells?
Bind to receptors in plasma membrane and enter via RME. Once in endosome, acidic pH allows viral membrane to fuse with endosomal membrane, releasing viral RNA into cell where can be translated and replicated by host cells machinery to make new virus particles E.g cholera toxin and diphtheria toxin which bind GM1 Ganglioside

ESA 2 SK (35 decks)

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