Abstract 14028: The Novel Z-Disk Protein Core-Binding Factor β is Essential for Cardiac Function
Cardiac mechanosensing and mechanotransduction are essential to adapt the force of contraction to changing hemodynamic needs. The Z-disk hosts specific sensor and transducer proteins that detect mechanical stress and translate it into downstream signaling cascades. We here identified the novel transcription cofactor Core-binding Factor β (CBFβ), which is highly expressed in nuclei and Z-disks of cardiomyocytes. By a reverse genetic approach in zebrafish, we show that CBFβ is required for Z-disk integrity and cardiomyocyte contractility. Consequently, CBFβ-deficient zebrafish develop progressive heart failure and skeletal myopathy (86% of injected embryos; n=100). Since we find multiple AP-1 binding sites in the promoter region of CBFβ, we next isolated the zebrafish ortholog of JunB, member of the AP-1 transcription factor complex. In JunB-morphant zebrafish, which show a heart failure phenotype similar to that of CBFβ-deficient zebrafish, transcript and protein levels of CBFβ are severely reduced. Accordingly, overexpression of CBFβ can reconstitute cardiac contractility in JunB-morphants, demonstrating for the first time an important role of JunB-CBFβ signaling for maintaining cardiomyocyte architecture and function.
- © 2010 by American Heart Association, Inc.