Neuregulin1 signaling targets SRF and CREB and activates the muscle spindle-specific gene Egr3 through a composite SRF-CREB-binding site.

摘要: Muscle spindles are sensory receptors embedded within muscle that detect changes in length. Each spindle is composed of specialized fibers, known as intrafusal along with the endings axons from neurons innervate these fibers. Formation requires neuregulin1 (NRG1), which released by axons, activating ErbB cells contacted. In cells, transcription factor Egr3 transcriptionally induced NRG1, turn activates various target genes involved forming fibers spindles. The signaling relay NRG1–ErbB pathway acts to induce presumably critical for formation but most part has not been determined. current studies, we examined, using cultured transcriptional regulatory mechanisms responds NRG1. We identified a composite element gene, consisting adjacent sites bind cAMP response binding protein (CREB) and serum (SRF), role NRG1 responsiveness. SRF also influences basal expression unstimulated myotubes, absence element, CREB expression. show signaling, SRF, on coactivators myocardian-related (MRTF)-A MRTF-B, activate SRF-mediated transcription, stimulating their translocation cytoplasm nucleus. phosphorylated, contribute its activation, These results suggest induces spindle-specific gene activity SRF.