Long-Term Biased β-Arrestin Signaling Improves Cardiac Structure and Function in Dilated Cardiomyopathy

BACKGROUND: responsiveness in a model of familial dilated cardiomyopathy and improve cardiac function and morphology. METHODS: response of detergent-extracted fiber bundles, and used proteomic approaches to understand changes in posttranslational modifications of proteins that may explain functional changes. We also assessed signaling pathways altered in vivo and by using isolated myocytes. RESULTS: responsiveness, which was depressed in untreated Tm-E54K mice. We attributed these changes to increased MLC2v and MYPT1/2 phosphorylation seen only in TRV120067-treated mice. We found that the functional changes were attributable to an activation of ERK1/2-RSK3 signaling, mediated through β-arrestin, which may have a novel role in increasing MLC2v phosphorylation through a previously unrecognized interaction of β-arrestin localized to the sarcomere. CONCLUSIONS: response via β-arrestin signaling pathways.