M&R 6.2 - Receptor Mediated Endocytosis Flashcards Preview

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Flashcards in M&R 6.2 - Receptor Mediated Endocytosis Deck (25):

What is receptor mediated endocytosis?

The selective internalisation of molecules due to activation of specific receptors


What is the mechanism for endocytosis?

- Cell surface membrane of the vesicle fuses with the cell surface membrane of the cell

- Both membranes merge therefore releasing the molecule


Describe the structure of a low density lipoprotein

- Hydrophobic core made from: Triacylglycerols and cholesterol esters

- Surface coat made from: phospholipids, cholesterol and Apoprotein B


What kind of receptor do cells that require cholesterol synthesis? Where are these receptors located?

- LDL receptors that specifically recognise apoprotein B

- Located directly over Clathrin Coated Pits (cover ~2% of the cell surface)


What happens when LDL binds to the receptors?

- Pit invaginates which encases the receptor and the LDL

- Then uncoats using energy from ATP

- Fuses with large, smooth vesicles (endosomes)


What is an endosome?

A compartment for the uncoupling of the receptor and the ligand (CURL)


What is the significance of the endosome having a lower pH than the cytoplasm? How is this maintained

- Decreases the affinity of the LDL receptor for the LDL which causes them to dissociate

- Maintained by the ATP dependent H+ pump


What happens to the receptor once it has dissociated from the LDL?

- Moves into a separate area of the endosome

- Buds off

- Recycled to the plasma membrane


What happens to the LDL once it has dissociated from the receptor?

- Endosome containing the LDL fuses with a lysosome

- Lysosome hydrolyses LDL

- Releases free cholesterol to the cell (along with esters)


Describe 3 mutations that can cause hypercholesterolaemia

- LDL receptors aren't above clathrin coated pits (cover entire surface rather than 2%) due to a deletion at the c-terminal - causes no interaction

- Mutation to receptor binding site = no LDL uptake

- Receptor deficiency due to mutation = less LDL uptake


How is transferrin formed in circulation?

- 2x Fe3+ bind to Apotransferrin = Transferrin


How is transferrin brought into the cell?

- Binds to a high affinity transferrin receptor on CSM

- Take in similarly to LDL (coated pit, then uncoated and fuses with endosome)

- pH competes for binding with transferrin which causes Fe3+ to be released (used with Hb)

- Apoferrin has a high affinity for the receptor at a lower pH so stays bound


What happens to the transferrin receptor after dissociation?

- Recycled to the plasma membrane

- Apoferrin is released when pH returns to 7


How does RME differ with insulin receptors? Why?

- The receptors ONLY congregate over the Clathrin coated ONCE THE AGONIST HAS BOUND

- Binding causes a conformational change that allows receptor to be recognised by the pit


What happens to the insulin-receptor complex when in the endosome?

- Remains bound

- Targeted by lysosomes for degradation (receptor and insulin are degraded so receptor isn't recycled)


What is the significance of uptake of occupied insulin receptors?

- Reduces number of insulin receptors on CSM

- Desensitised to the constant high concentration of insulin in circulation


Describe the development of type 2 diabetes

- Increased blood glucose levels means more insulin is secreted by beta cells

- Causes a down regulation of receptors (= resistance) which decreases the response to insulin

- Decreases glucose uptake so more is produced by the liver = HYPERGLYCAEMIA

- Less glucose transport, more insulin resistance

- Coupled with impaired beta cell function

- Resistance + deficiency = Type 2 diabetes


What is transcytosis?

Transport of ligand + receptor ACROSS THE CELL


Give 2 examples of transcytosis

- Maternal immunoglobulin to the foetus via the placenta

- Immunoglobulin A (IgA) from the circulation to bile in the liver


What is the affect of pH on IgA

- Has no effect

- Budding off of vesicle contains both receptor & ligand


What happens during the transport of IgA to the bile?

- Happens in a transfer vesicle (still bound)

- Proteolytic cleavage of the receptor leaves a small amount of the receptor bound to the ligand (secretory component)


Which method is used by all mechanisms of RME?


- Compartment for the uncoupling of the receptor and the ligand (endosome)


How can RME be exploited by viruses/toxins?

- Binds to receptor and is internalised in the same way as a metabolite

- Lower pH of the endosome causes a conformational change of enveloping proteins therefore exposing hydrophobic domains

- Viral membrane can fuse with the endosomal membrane


What happens after the fusion of the viral membrane with the endosomal membrane?

- Virus releases its own RNA into the cell

- Cell replicates itself and viral RNA to form a new virus


Give an example of TWO toxins that can exploit RME

- Cholera toxin

- Diptheria toxin

(Both bind to GM1 ganglioside)

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