M&R Receptor structure and mediated endocytosis Flashcards
What is a receptor?
What is a ligand?
A molecule that recognises a specific ligand or family of ligands and in which a response to ligand binding brings about regulation of a cellular process.
Any molecule that binds specifically to a receptor site. A ligand can be an agonist or antagonist (prevents agonist binding, NOT switching off the receptor).
What are the ways in which an extracellular signal can be traduced into an intracellular signal?
Give examples of each
- Membrane bound receptors with integral ion channels
e. g. nAChR with gated Na+, K+ channel - Membrane bound receptors with integral enzyme activity e.g. PDGF receptor linked to tyrosine kinase
- Membrane bound receptors that couple to effectors through transducing proteins
e. g. G protein coupled receptors, such as adrenaline binding to beta adrenoreceptors activates adenylyl cyclase - Intracellular receptors
e. g. transcription regulators, need h phobic signalling molecule like steroid hormones. Slow action because they rely of transcription and translation
Define:
Phagocytosis
Pinocytosis
Endocytosis
Phagocytosis is the internalisation of particulate matter via a ‘membrane zippering’ mechanism
Pinocytosis is the invagination of the plasma membrane to form a vesicle to uptake extracellular solutes and retrieve plasma membrane.
Endocytosis is the selective internalisation of molecules into the cell by binding to specific cell surface receptors
Describe the uptake of cholesterol as an example of receptor mediated endocytosis
(An example of metabolite uptake)
LDLs have Apoprotein B
Cells that need cholesterol synthesise surface LDL-receptors that recognise ApoB
These receptors are in clusters over CLATHRIN coated pits (pits form spontaneously)
LDL binds to the receptors and the pit invaginates to form coated vesicles
The vesicles are uncoated (requires ATP) and fuse with endososmes
The endosome pH is low (maintained by proton pump)
At this pH LDL has low affinity for the particle so they dissociate to release the LDL
The endosome is therefore known as CURL (Compartment of Uncoupling Receptor and Ligand)
The receptor is recycled back to the plasma membrane and the endosomes containing LDL fuse with lysosomes to hydrolyse the cholesterol.
What are triskelions?
Coat structures made of hexagons and pentagons
Hexagonal and pentagonal structures form clathrin triskelions
What are the mutations in the LDL receptor in hypercholesterolaemia?
Non functioning receptor - mutation to LDL binding site
Receptor binding normal - there could be a deletion that results in the LDL receptors not interacting with the clathrin coat so they are distributed over the whole cell surface instead of being clustered over the pits
Receptor deficiency - a mutation that prevents expression of the LDL receptor
Describe the uptake of Fe3+ as an example of receptor mediated endocytosis
(An example of metabolite uptake)
Two Fe3+ ions bind to apotransferrin to form transferrin in circulation
Transferrin binds to transferrin receptor and is internalised (similar to the way LDL is)
In the endosome the Fe3+ ions are released leaving apotransferrin still associated with the receptor
The complex is recycled back to the plasma membrane, where at physiological pH they dissociate
Describe the uptake of occupied insulin receptors as an example of receptor mediated endocytosis
(An example of receptor down-regulation)
Insulin receptors only congregate over the clathrin coated pits WHEN THEIR AGONIST IS BOUND
Insulin binding produces a conformational change that makes the receptors recognisable to the pits
In the endosome the insulin remains bound to the receptors and the complex is targeted to lysosomes for degradation
This mechanisms allows for a reduction in the number of insulin receptors on the surface so the cell becomes desensitised to a continued high circulating insulin conc
What is transcytosis?
An example of transfer of large molecules across the cell
Ligands remain bound to their receptor and are transported across the cell.
e. g. Maternal immunoglobulins transferred to the foetus via the placenta
e. g. Immunoglobulin A is transferred from the circulation to bile in the liver. During transported the receptor is cleaved, releasing IgA with a ‘secretory component’ of the receptor still attached
How do membrane enveloped viruses enter the cell?
They take advance of receptor mediated endocytosis by binding to receptors on the plasma membrane
In the endosome the acidic pH allows the viral membrane to fuse with the endosomal membrane, the viral RNA is released into the cell where it is translated by the host cells machinery
e.g. Cholera, Diptheria
Whats the difference between homologous and heterologous desensitisation?
Homologous desensitisation is when the receptor decreases its response due to prolonged high agonist concentration.
Heterologous desensitisation is when the receptor decreases its response to all agonists as a result of high concentration of one agonist.
Explain the process of desensitisation of a B adrenoreceptor (example of gpcr)
homologous desensitisation
- Agonist binds to receptor causing it to become activated
- Beta adrenergic receptor kinase is activated and phosphorylates C terminal of B2 receptor
- This phosphorylation causes B-arrestin to have increased affinity for the receptor, it causes uncoupling of the g protein from the receptor causing desensitisation
