Conformational activation of radixin by G13 protein α subunit

Abstract

G13 protein, one of the heterotrimeric guanine nucleotide-binding proteins (G proteins), regulates diverse and complex cellular responses by transducing signals from the cell surface presumably involving more than one pathway. Yeast two-hybrid screening of a mouse brain cDNA library identified radixin, a member of the ERM family of three closely related proteins (ezrin, radixin, and moesin), as a protein that interacted with Gα13. Interaction between radixin and Gα13 was confirmed by in vitro binding assay and by co-immunoprecipitation technique. Activated Gα13 induced conformational activation of radixin, as determined by binding of radixin to polymerized F-actin and by immunofluorescence in intact cells. Finally, two dominant negative mutants of radixin inhibited Gα13-induced focus formation of Rat-1 fibroblasts but did not affect Ras-induced focus formation. Our resets identifying a new signaling pathway for Gα13 indicate that ERM proteins can be activated by and serve as effectors of heterotrimeric G proteins.