Session 6 - Receptor-mediated endocytosis Flashcards
Describe phagocytosis after receptor activation
- Cell extends pseudopods, permitting further receptor interactions and membrane evagination
- Particle internalisation occurs through ‘membrane zippering’
- Phagosome then fuses with lysosome, forming secondary lysosome
- Contents digested by hydrolases and proteases
What is pinocytosis?
-Invagination of the PM to form a lipid vesicle to permit uptake of impermeable extracellular solutes and retrieval of PM
What is receptor-mediated endocytosis?
-The selective internalisation of molecules into the cell by binding to specific cell-surface receptors
What activates phagocytosis of a particle?
-Binding to receptors on the phagocyte
What is an LDL?
-Core of cholesterol esterified to FA, surrounded by a lipid monolayer containing phospholipids, cholesterol and apoB
Describe receptor-mediated endocytosis using LDL
- LDL receptor recognises ApoB
- Spontaneous coated pit invagination
- Pinching off to form an internal coated vesicle with ligand and receptor
- Coated vesicle is uncoated by an ATP-dependant uncoating protein
- The uncoated vesicle fuses with a larger smooth vesicle (endosome)
- LDL:LDL receptor dissociation
- LDL receptor recycled; LDL endosome fuses with lysosome where hydrolase enzymes are present
- Cholesterol is hydrolysed from the esters and released into the cell
Why does the LDL receptor dissociate from LDL when the vesicle fuses with the endosome
-The pH in the endosome is maintained between 5.5 and 6.0 by an ATP-dependant proton pump and causes the receptor to have low affinity for LDL so it dissociates
Where is the LDL receptor recycled to after endocytosis?
- Back to the PM
- Enters golgi apparatus and secretory pathway
Where are LDL receptors on PM?
-Localised over clatherin-coated pits
How does receptor-mediated endocytosis contribute to the uptake of Fe3+?
- Two Fe3+ bind to apotransferrin in the circulation
- Transferrin binds to transferrin receptor and is internalised through spontaneous clathrin coated pits forming vesicles
- In the endosome, the Fe3+ ions are released from apotransferrin
- Apotransferrin remains associated with the transferrin receptor
- Complex is sorted within CURL for recycling back to the PM
- Back at pH 7.4 apotransferrin dissociates
How does receptor-mediated endocytosis allow the passage of large molecules through PM?
- Ligand remains bound to its receptor and is transported across the cell eg maternal immunoglobulins via the placenta
- During transport receptor is proteolytically cleaved, resulting in the release of the immunoglobulin with a bound ‘secretory component’ from the receptor
How does receptor mediated endocytosis control insulin receptor number at the cell surface
- Insulin receptors only congregate over a clathrin pit when insulin is bound
- Internalisation of insulin and its receptor
- Fusion with endosome, insulin remains bound to receptor and whole complex is targeted to the lysosome for destruction
- Reduces receptor number at surface as they take a few hours to produce
- This desensitises the cell to the high conc of insulin
How does receptor-mediated endocytosis allow entry of membrane-enveloped viruses?
- Membrane enveloped viruses exploit this pathway
- Bind to receptors on PM
- RME through clathrin pits
- Once in the endosome, the acid pH is favourable and the virus membrane is able to fuse with the endosomal membrane
- The viral RNA is released into the cell where it can be translated and replicated into new viral particles
What are COP I and COP II?
-Other coat proteins
What are the 4 modes of receptor mediated endocytosis, based on the fate of the ligands and receptors?
1- Receptor recycled-ligand degraded (LDL)
2-Receptor recycled-Ligand recycled (Transferrin)
3-Receptor degraded-Ligand degraded (Insulin)
4-Receptor transported-Ligand transported (maternal igG)
