TRAFFICKING Flashcards
What fidelity to targets have to their destination?
High fidelity.
Transport vesicles are coated. What can their coats be made up of?
Clathrin
COPI
COPII
Newly made proteins can be translocated into organelles either co or post translationally. What does this mean?
Co translational translocation means that as the protein is being translated it is also being translocated into the ER of the lumen.
Post translational means the protein is translocated after being translated.
How leaky is fusion of vesicles onto membranes?
Not at all.
What is the function of SNAREs?
They provide specificity of fusion and ensures the correct vesicle fuses with the correct target membrane.
What does the Clathrin structure look like?
All protein coats are visible through electron microscopy.
Clathrin is distinction by its hexagonal protein arrays.
What is ER translocation?
movement of newly made proteins from the cytosol to the ER.
Where does cotranslational translocation occur more frequently?
The RER.
What is ‘The Signal Hypothesis’?
If a protein has a series of amino acids encoding an ER signal sequence, it can be translated and cotranslated into the ER
What is the process of translocation of a soluble protein?
A signal sequence at the end terminus (a stop transfer of the chain embeds into the translocator protein in the ER membrane. The signal sequence acts as a tether, anchoring the polypeptide chain allowing it to enter the ER lumen. A signal peptidase cleaves the signal sequence, releasing the sequence of amino acids into the ER lumen. Now the protein can be folded into the correct tertiary structure, in the ER lumen.
What is the process of insertion of membrane proteins into the ER membrane?
The polypeptide chain is fed through the open pore.
A stop transfer sequence on the polypeptide signals to the translocator to close, preventing further translocation. The sequences acts as a TMSD, anchoring the protein in the membrane.
A signal peptidase cuts off the signal peptide.
What is a type 1 membrane protein?
Amino terminus is translocated into the ER lumen.
What is a type 2 membrane protein?
Carboxyl terminus is translocated into the ER lumen.
What is the function of a chaperone protein?
Ensure proper protein folding.
What parts of the cell are rich in chaperones?
The ER lumen.
What is BiP?
BiP is a chaperone protein in the lumen of the ER that associates with newly made antibody molecules. BiP ensures that antibodies stay in the lumen until they are correctly assembled. After correct assembly, antibodies are packaged into vesicles for transport.
Defects in folding give rise to disease. Give an example.
Cystic Fibrosis
What does detection of misfolded proteins give rise to?
The Unfolded Protein Response
What is the Unfolded Protein Response?
Recognises that there are too many proteins in the ER lumen and the chaperone system is saturated.
Increases synthesis of ER chaperones and decreases the rate of protein synthesis.
Orkambi is used to treat Cystic Fibrosis?
Combination drug of a chaperon and a channel opener.
What is Gaucher’s disease?
Mutations in lysosomal enzymes required for glucosylceramide metabolism.
What can liver damage be caused by in terms of failed trafficking?
Mutant protein is not degraded and accumulates in hepatocytes.
Carbamazepine can be used to increase autophagy.
How is emphysema caused?
Deficiency of secretion of alpha1-antitrypsin.
Failure to inactivate neutrophil elastase in the lung.
What is the cause of hypothydroidism in terms of trafficking?
Production of mutant thyroglobulin.
This causes massive proliferation in the ER in attempt to secrete normal amounts of the hormone.
