Control of the Cystic Fibrosis Transmembrane Conductance Regulator by αGi and RGS Proteins

Abstract

The cystic fibrosis transmembrane conductance regulator (CFTR) has been shown previously to be regulated by inhibitory G proteins. In the present study, we demonstrate inhibition of CFTR by αGi2 and αGi1, but not αG0, in Xenopus oocytes. We further examined whether regulators of G protein signaling (RGS) proteins interfere with αGi-dependent inhibition of CFTR. Activation of CFTR by IBMX and forskolin was attenuated in the presence of αGi2, indicating inhibition of CFTR by αGi2 in Xenopus oocytes. Coexpression of the proteins RGS3 and RGS7 together with CFTR and αGi2 partially recovered activation by IBMX/forskolin. 14-3-3, a protein that is known to interfere with RGS proteins, counteracted the effects of RGS3. These data demonstrate the regulation of CFTR by αGi in Xenopus oocytes. Because RGS proteins interfere with the G protein-dependent regulation of CFTR, this may offer new potential pathways for pharmacological intervention in cystic fibrosis.