Receptors in Cell Signalling - 6.2 Flashcards
How is membrane added to the plasma membrane?
Via the exocytotic, secretory pathway from the Endoplasmic Reticulum (adds membrane to surface)
What is the process by which membrane is removed from the plasma membrane?
Endocytosis
What cells initiate phagocytosis?
Macrophages and neutrophils
Outline the process of phagocytosis
- 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
What is pinocytosis?
he invagination of the plasma membrane to form a lipid vesicle
What does pinocytosis allow to happen?
permits the uptake of impermeable extracellular solutes and retrieval of plasma membrane.
What two forms can pinocytosis take?
fluid-phase and receptor mediated endocytosis.
What is receptor mediated endocytosis?
Specific binding of molecules to cell surface receptors permits the selective uptake of substances into the cell.
A major example is uptake of cholesterol
What are low density lipoproteins?
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
What do animal cells which require cholesterol do?
Synthesis LDL - Receptors that recognise Apoprotein B
Where are LDL receptors located in cells?
Located in clusters over Clathrin coated pits that cover approximately 2% of cell surface. These pits form spontaneously beneath LDL receptors.
How does LDL enter cells?
- 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
How does the LDL receptor decouple from the LDL particle in the endosome?
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.
What is another name for the endosome?
Compartment for the Uncoupling of Receptor and Ligand (CURL).
What happens to receptors after decoupling?
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
What happens to the LDL in the endosome once decoupled from the receptor?
The endosomes containing the LDL fuse with lysosomes, and the cholesterol is hydrolysed from the esters and released into the cell.
What are three mutation which may affect the LDL receptor in hypercholesterolaemia?
Non-Functioning Receptor
Receptor Binding Normal
Receptor Deficiency
How does a non-functioning receptor cause hypercholesterolaemia?
If there is a mutation to the LDL binding site of the LDL-Receptor, it will prevent the binding and uptake of LDL.
How can hypercholesterol aemia occur even if receptor binding is normal?
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%.
How can a receptor defiency cause hypercholesterolaemia?
A deficiency caused by a mutation that prevents expression of the LDL-Receptor.
Give another example of receptor mediated endocytosis, other than LDL
Transferrin
What occurs in transferrin receptor mediated endocytosis?
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
What occurs when transferrin reaches the acidic endosome?
The Fe3+ ions are released
What happens to Apoptransferring after Fe3+ dissociation at endosome?
- 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.
How are insulin receptors different to both LDL and Transferrin receptors?
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.
What happens to insulin in the endosome?
In the endosome Insulin remains bound to the receptor and the complex is targeted to the lysosomes for degradation.
What does the degradation of the insulin-receptor complex allow for?
the reduction in the number of insulin receptors on the membrane surface, desensitising the cell to a continued presence of high circulating insulin concentration.
What can happen to some ligands which remain bound to their receptors?
They may be transported across the cell in the process of transcytosis
Give an example of transcytosis
Transfer of immunoglobulin A (IgA) from the circulation to bile in the liver or maternal immunoglobulins to the foetus via the placenta.
What occurs during transport of IgA in transcytosis to bile in the liver?
the receptor is cleaved, resulting in the release of immunoglobulin with a bound ‘secretory component’ derived from the receptor.
Whatis common to all proteins that undergoe endocytosis?
Ligands enter the cell via the same Clathrin coated pits and the pathway from coated pits to the endosome
What differs between proteins which undergo endocytosis?
destination of the internalised receptor and ligand
How are receptors targeted to different cellular destinations?
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.
What happens in mode 1 of receptor mediated endocytosis (LDL) is an example?
Receptor is recycled, Ligand is degraded. Function is metabolite uptake.
What happens in mode 2 of receptor mediated endocytosis? (example is transferrin)
Receptor is recycled, ligand is recycled. Function is metabolite uptake
What happens in mode 3 endocytosis? (insulin and immune complexes)
Receptor degraded, Ligand degraded. Function is receptor down regulation or, in the case of immune complexes, removale from circulation of foreign anti-gen.
What happens in mode 4 endocytosis? (examples include IgA and Maternal IgG
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)
For the following modes of transport, gives exapmples Mode 1 Mode 2 Mode 3 Mode 4
1 - LDL
2 - Transferrin
3 - Insulin, immune complexes
4 - Maternal IgG, IGA
What pathogens can exploit process endocytosis?
Membrane enveloped viruses and some toxins
What is the process by which membrane enveloped viruses enter cell?
- 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.
What two toxins can enter cell?
Cholera toxin, Diptheria toxin
