CPPS 325 - CFTR Do mutations in CFTR modulate membrane lipids Exam

CPPS 325 - CFTR Do mutations in CFTR
modulate membrane lipids Exam



Most common CFTR mutation - Answer ΔF508
- Impacts 80-90% of people with CF

What does ΔF508-CFTR do? - Answer It causes CFTR missfolding
- CFTR is retained in the ER due to it's inability to escape the ER quality control
- Targeted for lysosomal degredation

ΔF508-CFTR that make it to the PM - Answer Only 5%
- CFTR will suffer reduced stability and is internalized prematurely

ΔF508-CFTR at the PM - Answer Doesn't partition inside lipid rafts
- little to no clusters

ΔF508-CFTR in the ER - Answer Majority of the ΔF508-CFTR is retained inside the ER
due to protein misfolding

ΔF508-CFTR with Thaps - Answer Thaps (cell stressor) doesn't influence clustering
- It doesn't cause ΔF508-CFTR to be incorporated inside ceramide rich platforms

VX809 - Answer CFTR folding corrector

ΔF508-CFTR with VX809 - Answer VX809 doesn't restore ΔF508-CFTR clustering or
platform formation

VX770 - Answer CFTR functional potentiator
- Potentiators are CFTR modulators that hold the gate open so chloride can flow
through the cell membrane

ΔF508-CFTR with VX8770 - Answer VX770 doesn't restore ΔF508-CFTR cluster
formation

DA - Answer Degree of aggregation
- # of CFTR channels per cluster

DA of Normal CFTR vs ΔF508-CFTR - Answer DA of ΔF508-CFTR is 5x smaller than
Wt-CFTR
- There are less ΔF508-CFTR clustered inside lipid rafts