Control of the cystic fibrosis transmembrane conductance regulator by alpha G(i) and RGS proteins

The cystic fibrosis transmembrane conductance regulator (CFTR) has been sho wn previously to be regulated by inhibitory G proteins. In the present stud y, we demonstrate inhibition of CFTR by alphaG(i2) and alphaG(i1), but not alphaG(0), in Xenopus oocytes. We further examined whether regulators of G protein signaling (RGS) proteins interfere with alphaG(i)-dependent inhibit ion of CFTR. Activation of CFTR by IBMX and forskolin was attenuated in the presence of alphaG(i2), indicating inhibition of CFTR by alphaG(i2) in Xen opus oocytes. Coexpression of the proteins RGS3 and RGS7 together with CFTR and alphaG(i2) partially recovered activation by IBMX/forskolin. 14-3-3, a protein that is known to interfere with RGS proteins, counteracted the eff ects of RGS3. These data demonstrate the regulation of CFTR by alphaG(i) in Xenopus oocytes. Because RGS proteins interfere with the G protein-depende nt regulation of CFTR, this may offer new potential pathways for pharmacolo gical intervention in cystic fibrosis. (C) 2001 Academic Press.