STARS, a Striated Muscle Activator of Rho Signaling and Serum Response Factor-dependent Transcription

Changes in actin dynamics influence diverse cellular processes and couple the actin-based cytoskeleton to changes in gene transcription. Members of the Rho GTPase family regulate cytoskeletal organization by stimulating actin polymerization and stress fiber formation when activated by extracellular signaling. The transcriptional activity of serum response factor (SRF) is stimulated in response to changes in actin dynamics and Rho signaling, but the proteins that mediate this phenomenon have not been fully identified. We describe a novel, evolutionarily conserved actin-binding protein, called STARS (striated muscle activator of Rho signaling), that is expressed specifically in cardiac and skeletal muscle cells. STARS binds to the I-band of the sarcomere and to actin filaments in transfected cells, where it activates Rho-signaling events. STARS stimulates the transcriptional activity of SRF through a mechanism that requires actin binding and involves Rho GTPase activation. STARS provides a potential mechanism for specifically enhancing Rho-dependent transcription in muscle cells and for linking changes in actin dynamics to gene transcription.