6. Endocytosis Flashcards
What are coated pits?
Coated pits are basket-like structures on the CYTOSOLIC face of the cell membrane.
They are made of pentagons and hexagons formed from triskelions which assemble spontaneously. TRISKELIONS consist of 3 heavy clathrin chains and 3 light clathrin chains.
ADAPTOR PROTEINS are integral membrane proteins which attach the clathrin and receptors to the plasma membrane.
What is the difference between phagocytosis and pinocytosis?
PHAGOCYTOSIS only occurs in SPECIALISED CELLS. It requires binding of particles to RECEPTORS. Pseudopods extend from the cell and uptake occurs by EVAGINATION using a membrane-zippering mechanism.
PINOCYTOSIS occurs in ALL CELLS. Uptake occurs by INVAGINATION and forms a LIPID VESICLE. There are two subtypes:
a) FLUID PHASE PINOCYTOSIS
b) RECEPTOR MEDIATED ENDOCYTOSIS
Describe how receptor mediated endocytosis occurs with relation to LDL uptake.
- RECEPTOR BINDING
(Apoprotein B binds with LDL receptor on a coated pit) - COATED PIT INVAGINATES, pinches off and forms coated vesicle.
- UNCOATING PROTEIN uncoats vesicles which requires ATP.
(coat proteins then spontaneously reform a coated pit) - ENDOSOME FUSES with uncoated vesicle
- LDL DISSOCIATES from receptor due to low pH (5.5-6.0) maintained by ATP-dependent proton pump.
- RECEPTORS RECYCLED to plasma membrane.
- LYSOSOMES fuse with endosomes containing LDLs and hydrolyse cholesterol esters into cholesterol and fatty acids.
What is another name for endosomes?
Endosomes are also called Compartment for Uncoupling of Receptor and Ligand (CURL).
A low pH (5.5-6.0) is maintained by an ATP-dependent Proton Pump which facilitates dissociation of ligand from receptor and hence the name.
What is the difference between transferrin and apotransferrin?
APOTRANSFERRIN is a transport protein required to carry ferric (Fe3+) ions in the circulation.
APOTRANSFERRIN describes the unbound transport protein. When two ferric ions bind with apotransferrin, the combination is called TRANSFERRIN.
Transferrin has greater affinity for the receptor at neutral pH at the plasma membrane thus it binds whereas apotransferrin has greater affinity for the receptor at acidic pH at the endosome. Therefore at the endosome, transferrin releases its ferric ions to become apotransferrin.
Describe what happens to transferrin bound to its receptor at the endosome.
At the low endosomic pH, apotransferrin has a higher affinity than transferrin to its the receptor. Therefore to become apotransferrin, the bound transferrin releases its ferric (Fe3+) ions.
a) Ferric ions are RELEASED into the cytoplasm
b) Apotransferrin bound to the transferrin receptor, is RECYCLED to the plasma membrane (where apotransferrin has low affinity for the receptor thus is released to sequester more ferric ions)
Why is the insulin receptor different from other receptors involved in receptor mediated endocytosis?
Insulin isn’t normally internalised - it exerts its effect by signal transduction at the plasma membrane via a tyrosine kinase linked receptor. This means the receptor isn’t normally located over coated pits.
However, when bound, the insulin receptor tends to congregate at coated pits therefore when insulin concentrations are high, receptor mediated endocytosis of insulin and its receptor occurs.
What happens to insulin at the endosome?
Insulin remains bound to its receptor and both are degraded by lysosomes.
This allows DOWN REGULATION of insulin receptors when extracellular insulin concentrations are too high. This is the model for DESENSITISATION of cells to insulin developed in type 2 diabetes mellitus.
Define transcytosis.
Transcytosis is the transport of ligands which REMAIN BOUND to receptors, across the cell.
Give TWO examples of transcytosis.
a) Transfer of MATERNAL IgG to foetus via the placenta.
b) Transfer of IgA from CIRCULATION TO BILE in the liver
(note: receptor is cleaved so IgA is released bound to a secretory component)
How do membrane enveloped viruses and some toxins exploit the receptor mediated endocytosis pathway?
- VIRAL ANTIGENS bind to receptors in coated pits and are internalised.
- UNFOLDING of MEMBRANE FUSION PROTEINS in endosomes.
- RELEASE OF RNA to produce viral proteins.
