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2 - Sarah's M&R > Receptors in Cell Signalling - 6.2 > Flashcards

Receptors in Cell Signalling - 6.2 Flashcards

1
Q

How is membrane added to the plasma membrane?

A

Via the exocytotic, secretory pathway from the Endoplasmic Reticulum (adds membrane to surface)

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2
Q

What is the process by which membrane is removed from the plasma membrane?

A

Endocytosis

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3
Q

What cells initiate phagocytosis?

A

Macrophages and neutrophils

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4
Q

Outline the process of phagocytosis

A
  • Particle binds to receptors in plasma membrane
  • Cell extends Pseudopods that permit further receptor interactions
  • Membrane invagination via a “membrane zippering” mechanism takes place
  • Internalised phagosomes fuse with lysosomes to form phagolysosomes in which the particulate material is degraded
  • Permits the clearance of damaged cellular materials and destruction of invading organisms
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5
Q

What is pinocytosis?

A

he invagination of the plasma membrane to form a lipid vesicle

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6
Q

What does pinocytosis allow to happen?

A

permits the uptake of impermeable extracellular solutes and retrieval of plasma membrane.

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7
Q

What two forms can pinocytosis take?

A

fluid-phase and receptor mediated endocytosis.

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8
Q

What is receptor mediated endocytosis?

A

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

A major example is uptake of cholesterol

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9
Q

What are low density lipoproteins?

A

Lipoproteins that originate in the liver and consist of a core of ccholesterol esters and TAGs, surrounded by phospholipids, cholesterol and a single protein species, apoprotein B

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10
Q

What do animal cells which require cholesterol do?

A

Synthesis LDL - Receptors that recognise Apoprotein B

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11
Q

Where are LDL receptors located in cells?

A

Located in clusters over Clathrin coated pits that cover approximately 2% of cell surface. These pits form spontaneously beneath LDL receptors.

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12
Q

How does LDL enter cells?

A
  • Bind to LDL receptors
  • Invaginated into cell via clathrin coated pit, form coated vesicles.
  • These vesicles are uncoated in a process that required ATP and fuse with larger, smooth vesicles called endosomes
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13
Q

How does the LDL receptor decouple from the LDL particle in the endosome?

A

The pH of the endosome is lower than that of the cytoplasm (5.5-6.0), maintained by an ATP-dependent proton pump. At this pH, the LDL receptor has a low affinity for the LDL particle and the two dissociate.

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14
Q

What is another name for the endosome?

A

Compartment for the Uncoupling of Receptor and Ligand (CURL).

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15
Q

What happens to receptors after decoupling?

A

The 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

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16
Q

What happens to the LDL in the endosome once decoupled from the receptor?

A

The endosomes containing the LDL fuse with lysosomes, and the cholesterol is hydrolysed from the esters and released into the cell.

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17
Q

What are three mutation which may affect the LDL receptor in hypercholesterolaemia?

A

Non-Functioning Receptor
Receptor Binding Normal
Receptor Deficiency

18
Q

How does a non-functioning receptor cause hypercholesterolaemia?

A

If there is a mutation to the LDL binding site of the LDL-Receptor, it will prevent the binding and uptake of LDL.

19
Q

How can hypercholesterol aemia occur even if receptor binding is normal?

A

Mutation, causing deletion of the C-terminal cytoplasmic domain, which prevents the interaction between the receptor and the Clathrin coat. The LDL-Receptors will be distributed over the entire cell surface instead of being concentrated in 2%.

20
Q

How can a receptor defiency cause hypercholesterolaemia?

A

A deficiency caused by a mutation that prevents expression of the LDL-Receptor.

21
Q

Give another example of receptor mediated endocytosis, other than LDL

A

Transferrin

22
Q

What occurs in transferrin receptor mediated endocytosis?

A

Two Fe3+ ions bind to Apoptransferrin to form Transferrin in the circulation.
Transferrin, but not Apoptransferrin, binds to the Transferrin Receptor at neutral pH and is internalised in a similar way to LDL

23
Q

What occurs when transferrin reaches the acidic endosome?

A

The Fe3+ ions are released

24
Q

What happens to Apoptransferring after Fe3+ dissociation at endosome?

A
  • At acidic pH of endosomethe Apoptransferrin 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 Apoptransferrin dissociates from the receptor again.
25
Q

How are insulin receptors different to both LDL and Transferrin receptors?

A

insulin receptors only congregate over Clathrin coated pits when their agonist is bound. Insulin binding. Induces a conformationalchange in the receptor that allows it to be recognised by the pit.

26
Q

What happens to insulin in the endosome?

A

In the endosome Insulin remains bound to the receptor and the complex is targeted to the lysosomes for degradation.

27
Q

What does the degradation of the insulin-receptor complex allow for?

A

the reduction in the number of insulin receptors on the membrane surface, desensitising the cell to a continued presence of high circulating insulin concentration.

28
Q

What can happen to some ligands which remain bound to their receptors?

A

They may be transported across the cell in the process of transcytosis

29
Q

Give an example of transcytosis

A

Transfer of immunoglobulin A (IgA) from the circulation to bile in the liver or maternal immunoglobulins to the foetus via the placenta.

30
Q

What occurs during transport of IgA in transcytosis to bile in the liver?

A

the receptor is cleaved, resulting in the release of immunoglobulin with a bound ‘secretory component’ derived from the receptor.

31
Q

Whatis common to all proteins that undergoe endocytosis?

A

Ligands enter the cell via the same Clathrin coated pits and the pathway from coated pits to the endosome

32
Q

What differs between proteins which undergo endocytosis?

A

destination of the internalised receptor and ligand

33
Q

How are receptors targeted to different cellular destinations?

A

By short amino acid motiffs.
These are recognised and and sorted within the CURL and sent to discrete regions of membrane, which they get to via transport vesicles.

34
Q

What happens in mode 1 of receptor mediated endocytosis (LDL) is an example?

A

Receptor is recycled, Ligand is degraded. Function is metabolite uptake.

35
Q

What happens in mode 2 of receptor mediated endocytosis? (example is transferrin)

A

Receptor is recycled, ligand is recycled. Function is metabolite uptake

36
Q

What happens in mode 3 endocytosis? (insulin and immune complexes)

A

Receptor degraded, Ligand degraded. Function is receptor down regulation or, in the case of immune complexes, removale from circulation of foreign anti-gen.

37
Q

What happens in mode 4 endocytosis? (examples include IgA and Maternal IgG

A

Receptor transported, ligand transported. Function is transfer of large molecules across cell.
(Maternal IgG provides maternal immunity to foetus via placenta, whereas IgA is transferred from circulation to bile)

38
Q 
For the following modes of transport, gives exapmples
Mode 1 
Mode 2
Mode 3
Mode 4
A

1 - LDL
2 - Transferrin
3 - Insulin, immune complexes
4 - Maternal IgG, IGA

39
Q

What pathogens can exploit process endocytosis?

A

Membrane enveloped viruses and some toxins

40
Q

What is the process by which membrane enveloped viruses enter cell?

A
  • adventitious binding to receptors in the plasma membrane
  • Once in the endosome, the acidic pH allows the viral membrane to fuse with the endosomal membrane,
  • releases the viral RNA into the cell where it can be translated and replicated by the host cell’s machinery to form new viral particles.
41
Q

What two toxins can enter cell?

A

Cholera toxin, Diptheria toxin

2 - Sarah's M&R (11 decks)

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