| First Author | Sitbon YH | Year | 2024 |
| Journal | iScience | Volume | 27 |
| Issue | 8 | Pages | 110591 |
| PubMed ID | 39211545 | Mgi Jnum | J:353613 |
| Mgi Id | MGI:7716036 | Doi | 10.1016/j.isci.2024.110591 |
| Citation | Sitbon YH, et al. (2024) Dual effect of N-terminal deletion of cardiac myosin essential light chain in mitigating cardiomyopathy. iScience 27(8):110591 |
| abstractText | We investigated the role of the N-terminus (residues 1-43) of the myosin essential light chain (N-ELC) in regulating cardiac function in hypertrophic (HCM-A57G) and restrictive (RCM-E143K) cardiomyopathy mice. Both models were cross-genotyped with N-ELC-truncated Delta43 mice, and the offspring were studied using echocardiography and muscle contractile mechanics. In A57GxDelta43 mice, Delta43 expression improved heart function and reduced hypertrophy and fibrosis. No improvements were seen in E143KxDelta43 compared to RCM-E143K mice. HCM-mutant pathology involved an impaired N-ELC tension sensor, disrupted N-ELC-actin interactions, an altered force-pCa relationship, and a destabilized myosin's super-relaxed state. Removal of the malfunctioning N-ELC sensor led to functional rescue in HCM-truncated mutant hearts. However, the RCM mutation could not be rescued by N-ELC deletion, likely due to its proximity to the myosin motor domain, affecting lever-arm rigidity and myosin function. This study provides insights into the role of N-ELC in the development and potential rescue of ELC-mutant cardiomyopathy. |
