Lecture 4 - CF and Small molecules 1 Flashcards
(34 cards)
CFTR is made up of…
12 TMDS
CFTR is divided…
into two groups of 6 TMDs
CFTR regulatory domain location and function
between the two subgroups and is where CFTR is phosphorylated by PKA
NBD1 and 2 are…
important for gating
what is the most common mutation and in what %?
F508del in 70-90% patients
CFTR class I
unstable mRNA, degraded before protein synthesis so no CFTR produced
CFTR class II
CFTR is made but does not reach the membrane due to misfiling leading to degradation
CFTR class II example
F508del
CFTR class III
CFTR enters membrane but PKA-mediated phosphorylation does not occur/channel does not respond to it. Decreased open probability
CFTR class IV
CFTR in membrane but it does not open as effectively - conduction
CFTR class V
mRNA partial reduction, so protein is made but there is less in the membrane
CFTR class VI
high turnover of CFTR, enters the membrane but amount of time in membrane is reduced
Sweat chloride diagnostic level
60mmolL-1
Severe mutations and symptoms
I=III, higher sweat chloride levels with pancreatic insufficiency
Carriers have…
50% normal CFTR levels
How much normal functioning CFTR is required for normal function?
15% hypothesised
ENaC and CFTR in the upper airway model
CFTR regulates ENaC
when one is open the other is closed
CF and upper airway model
less CFTR function, so more ENaC function than normal
enhanced sodium reabsorption results in exacerbation of loss of fluid
Upper airway model basolateral membrane proteins
Na+/K+ATPase
NKCC2
K+ channel
Alveolar model CFTR and ENaC
both absorbing no secreting
Alveolar model basolateral membrane proteins
K+/Na+ATPase
Cl-/K+ co-transporter
K+ channel
Distal sweat gland model CFTR and ENaC
CFTR drives chloride reabsorption
CFTR activated ENaC
Distal sweat gland and CFTR
CFTR is non-functional, no Cl- reabsorption
Loss of EnaC function
Distal sweat gland model basolateral membrane proteins
Na+/K+ATPase, CFTR and K+ channel
