Lecture 19 - Subverting trafficking in disease Flashcards
What side of the membrane are GPI anchored proteins found?
GPI anchored proteins are normally found in the lumen.
What is the result of the mutation that results in cystic fibrosis? (i.e why is cystic fibrosis symptoms the phenotype of this mutation?)
Cystic fibrosis results in a mis-folded protein and as a result the protein does not reach the surface and is not expressed.
How can expression of CFTR be induced to bypass the quality control pathway? Why is this not a 100% cure?
Expression of CFTR can be induced using curcumin. However, this therapy only causes expression of the faulty receptor that was being cleared by quality control pathway. i.e the receptor is still faulty but has some functionality.
*This rescue of this protein is induced by higher calcium levels in the cell.
What are methods by which pathogens can survive phagocytosis or endocytosis?
Escape: (eg all viruses and some bacteria) escape the phagosome or endosome.
Prevent lysosome fusion: (eg. many bacteria and mycobacterium.
Surviving in phagolysosome (eg many parasites.)
Many bacteria multiply in phagolysosomes. Legionella.
Listeria can escape from endosome and live in cytosol and use actin filaments from host cell to move around. It can use this actin to propel itself into other cells and to create holes in host cell. (in other words this bacterium is a cheeky cunt)
How do enveloped proteins enter and exit host cells?
Enveloped virions enter their host cells by fusing with the cell membrane. This results in uncoating of the virus in the cytosol. Viral proteins remain on the plasma membrane and this allows the viruses produced to bud from the membrane of the host cell.
Some viral proteins get phagocytosed and then release themselves at a low enough pH environment created by the endosomes they exist in.
How does HIV enter immune cells?
HIV enters immune cells via protein - protein interactions between gp120 and gp41. HIV interacts with CD40 and is tethered to a chemokine receptor. It fuses with the membrane via gp120 and gp41.
How does HIV prevent it’s detection by the immune system?
HIV inhibits the degradation of viral peptides and this results in decreased expression of antigen to cytotoxic T cells.
They will also interfere with antigen presenting proteins.
Why does HIV decrease the amount of CD4 receptors on the membrane?
NEF produced by HIV binds to AP-2 and cytosolic portion of CD4 and this results in endocytosis of the receptor preventing its expression.
