Lecture 8 Flashcards
Cystic fibrosis was first described in ____
1938
1983 - fundamental defect identified as abnromal ____-mediated regualtion of chloride transport (sweat ducts)
cAMP
the CFTR gene is about ___kb
there are __exons
90kb DNA
27 Exons
Its clear that certain exons code for specific ___ in the proteins that have a functional role
domains
The CFTR protein is a member of the ___superfamilty of membrane transporters
it is a ___channel protein (differs by _______, not active transport)
the opening and closing of the channel is regualted by ____-dependent phosphorylation
The CFTR protein is a member of the ABC superfamilty of membrane transporters
it is a chlorine channel protein (differs by diffusion, not active transport)
the opening and closing of the channel is regualted by cAMP-dependent phosphorylation
How many domains are in the CFTR protein?
what are they?
5 Domains
The ____terminal is anchored to trhe cytoskeleton and kept close to other proteins whihc influence CFTR functions, such as:
Carboxy terminal
Conductance
regulation of other channels (eg.epithelial sodium channel_
Signal transduction
localisation at apical plasma membrane
In the normal lung - movmeent of cholrine oins through CFTR channel is __ of the cell
out
from the cell into the ECS
In the sweat ducts - the movement, down the conc. gradient, is ___ the cell
into the cell
CF sweat duct block the entry of cl- into the cells - so the sweat tastes saltier
Missense, Frameshift, Splicing and Nonsense will be the ___ severe phrenotypes generally
the most severe phrenotypes generally
Most mutations are foudn in 4 different exons, typically to do with the _____ ______ domains
membrane spanning domains
What are the five classes of CFTR mutations?
and sixth
Class 6: Accelerated turnover from cell surface
F508del is a class __ mutaiton
is causes ______
mutant protein is then retained in the __
targeted for ________
F508del is a class II mutaiton
it causes misfolding
mutant protein is then retained in the ER
targeted for degradation
what are some treatments for the different class mutations?
Class I: often nonsense muations, compounds that allow ‘read through’ of mRNA are used
Class II: “correctors” to imporve processing
Class III: “potentiators” to activate protein
Class IV: Flavonoid compounds to augment channel function
Class V: often splicing mutations, increase levels of correctly spliced RNA
the pF508del mutaion involves the erradication of __________
phenylalanine
