Cystic Fibrosis Transmembrane Conductance Regulator - Location and Function

Location and Function

CFTR functions as a cAMP-activated ATP-gated anion channel, increasing the conductance for certain anions (e.g. Cl–) to flow down their electrochemical gradient. ATP-driven conformational changes in CFTR open and close a gate to allow transmembrane flow of anions down their electrochemical gradient. This in contrast to other ABC proteins, in which ATP-driven conformational changes fuel uphill substrate transport across cellular membranes. Essentially, CFTR is an ion channel that evolved as a 'broken' ABC transporter that leaks when in open conformation.

The CFTR is found in the epithelial cells of many organs including the lung, liver, pancreas, digestive tract, reproductive tract, and skin. Normally, the protein moves chloride and thiocyanate ions (with a negative charge) out of an epithelial cell to the covering mucus. Positively charged sodium ions follow these anions out of the cell to maintain electrical balance. This increases the total electrolyte concentration in the mucus, resulting in the movement of water out of cell by osmosis.

In epithelial cells with motile cilia lining the bronchus and the oviduct, CFTR is located on cell membrane but not on cilia. In contrast to CFTR, ENaC is located along the entire length of the cilia. These findings contradict a previous hypothesis that CFTR normally downregulates ENaC by direct interaction and that in CF patients, CFTR cannot downregulate ENaC causing hyper-absorption in the lungs and recurrent lung infections.

In sweat glands, CFTR defects result in reduced transport of sodium chloride and sodium thiocyanate in the reabsorptive duct and saltier sweat. This was the basis of a clinically important sweat test for cystic fibrosis before genetic screening was available.