Flashcards in 11. Principles of Receptor-Mediated Endocytosis Deck (27):
Internalisation of particulate matter.
Invagination of the the plasma membrane to form a vesicle, permits uptake of extracellular solutes.
The selective internalisation of molecules into the cell by binding to specific cell surface receptors.
How is cholesterol uptake not into a cell?
Using receptor mediated endocytosis.
What is the structure of low density lipoproteins?
Core of esterified cholesterol esters that are covered by a phospholipid and cholesterol mono layer and contain apoprotein B.
What are triskelions?
Coat structures made up of hexagons and pentagons. The hexagonal and pentagonal structures are formed from clathrin triskelions. Triskelions comprise 3 clathrin heavy chains and 3 light chains.
How are clathrin coats formed?
How are clathrin coats disassembled?
They're uncalled by an ATP-dependent uncoating protein.
What mutations affect the LDL receptor in hypercholestolaemia?
Non-functioning receptor so no binding of LDL but normal coated pits and internalisation.
Receptor binding normal but no internalisation even with LDL receptors distributed over whole cell surface but there is deletion of C-terminal cytoplasmic domain that prevents interaction with the clathrin clot.
Give a brief overview of receptor mediated endocytosis.
LDL attaches to a receptor in a coated pit. The pit invaginates to become a coated vesicle. It is uncoated by ATP-dependent uncoating and becomes an uncoated vesicle. Uncoated vesicle fuses with the endosome, where the pH is low inside but there are no lysosomal enzymes (prelysosomal). The endosome is the compartment of uncoupling of receptor and ligand as it dissociates the receptor outside due to acidic conditions. The endosome buds off as lysosomes. The receptors bud off and find their way back to the membrane.
What makes endosome prelysosomal?
They don't have any lysosomal enzymes.
What is the fate of the ligand and receptor in endocytosis of LDL?
Ligand is degraded, receptor is recycled.
What happens to the intracellular [59Fe] as the surface concentration drops?
What happens to the protein transferrin concentration intracellularly over time?
It increase for a short time but then decreases as the culture medium rises. This means the protein that carries Fe ions is recycled.
What do ferric ions bind to at pH7.0?
Apotranferrin to form ferrotransferrin.
What happens to the uncoated vesicles of Fe3+?
They bind to endosome, much like RME of LDL.
What is the fate of the ligand and receptor after endocytosis of transferrin?
Ligand is recycled and receptor is also recycled.
What is the fate of the ligand and receptor in endocytosis of insulin?
Ligand is degraded and receptor is also degraded.
What is the fate of ligands and receptors after endocytosis of immunoglobulin transcytosis?
Ligand is transported and receptor is also transported.
What's an example of receptor-mediated endocytosis Where the receptor is recycled and the ligand is degraded?
What's an example of receptor-mediated endocytosis where the receptor is recycled and the ligand is recycled too?
What's an example of receptor-mediated endocytosis where the receptor is degraded and ligand is degraded too?
What's an example of receptor-mediated endocytosis where the receptor is transported and the ligand is transported too?
Immunoglobulin A and G.
How is RME affected in type II diabetes?
Raised glucose through diet, means more insulin is secreted. If insulin is raised for a prolonged period, the receptors are down regulated so there are fewer receptors. This is an insulin resistance. So there is a reduced response to insulin and lower glucose uptake. The lack of insulin triggers glucose production and further hyperglycaemia and further down regulation.
How do membrane-enveloped viruses enter cells?
Using receptor-mediated endocytosis. They bind to cells by fortuitous association with cell receptors. Then enter cells via clathrin-coated pits and unfold hydrophobic domains in membrane fusion proteins in response to the acidic pH of the endosome. They use the pH to change the conformation of the protein to reveal finger like protrusions. This allows fusion into the endosome membrane and introduces the genetic material into the cytoplasm. The RNA genome is translated and reproduced and reforms on the membrane of the cell and buds off.
Which toxins can enter by RME?
Cholera toxin, diphtheria toxin. Both bind to GM1 ganglioside.