SIGNAL-TRANSDUCTION OF A G-PROTEIN-COUPLED RECEPTOR IN CAVEOLAE - COLOCALIZATION OF ENDOTHELIN AND ITS RECEPTOR WITH CAVEOLIN

Caveolae are small invaginations of the plasma membrane 50-100 nm in d iameter. Since calcium channels, inositol 1,4,5-trisphosphate receptor s, and heterotrimeric GTP-binding proteins (G proteins) are localized in caveolae, they may participate in signal transduction by G protein- coupled receptors. Here we show that the G protein-coupled endothelin receptor subtype A (ET(A)) and its bound endothelin ligand are found i n plasma membrane caveolae. ET(A) and its bound ligand coimmunoprecipi tate with caveolin, a structural component of caveolae, in extracts of tells expressing transfected ET(A) receptors. Confocal fluorescence m icroscopy shows colocalization of ET(A) receptors and caveolin in micr opatches at or near the plasma membrane, in the absence of endothelin ligands. These observations demonstrate a functional role for plasma m embrane caveolae in signal transduction by this G protein-coupled rece ptor.