WHAT WE KNOW AND WHAT WE DO NOT KNOW ABOUT CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR

The cystic fibrosis transmembrane conductance regulator (CFTR) is a cA MP-regulated chloride channel that resides in the apical membrane of m any epithelial cells. Channel opening requires phosophorylation of ser ine residues in an intracellular regulatory domain by protein kinase A and as the binding and hydrolysis of ATP by intracellular nucleotide binding domains. Besides conducting the chloride ion, CFTR also regula tes the function of other membrane proteins, directly or indirectly, n otably the outwardly rectifying chloride channel and the epithelial so dium channel. The disease cystic fibrosis is caused by mutations in CF TR, which can result in defective protein production, defective proces sing and degradation in the endoplasmic reticulum, or defective channe l pore properties or gating properties.