Dual effect of N-terminal deletion of cardiac myosin essential light chain in mitigating cardiomyopathy.
Biochemical mechanism
Medical biochemistry
Molecular medicine
Pathophysiology
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
16 Aug 2024
16 Aug 2024
Historique:
received:
10
03
2024
revised:
14
06
2024
accepted:
23
07
2024
medline:
31
8
2024
pubmed:
31
8
2024
entrez:
30
8
2024
Statut:
epublish
Résumé
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 Δ43 mice, and the offspring were studied using echocardiography and muscle contractile mechanics. In A57G×Δ43 mice, Δ43 expression improved heart function and reduced hypertrophy and fibrosis. No improvements were seen in E143K×Δ43 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.
Identifiants
pubmed: 39211545
doi: 10.1016/j.isci.2024.110591
pii: S2589-0042(24)01816-9
pmc: PMC11357882
doi:
Types de publication
Journal Article
Langues
eng
Pagination
110591Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL143830
Pays : United States
Organisme : NHLBI NIH HHS
ID : R56 HL146133
Pays : United States
Informations de copyright
© 2024 The Author(s).
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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