Myosin regulatory light chain phosphorylation enhances cardiac β-myosin in vitro motility under load

Anastasia Karabina, Katarzyna Kazmierczak, Danuta Szczesna-Cordary, Jeffrey R. Moore

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Abstract Familial hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy and myofibrillar disarray, and often results in sudden cardiac death. Two HCM mutations, N47K and R58Q, are located in the myosin regulatory light chain (RLC). The RLC mechanically stabilizes the myosin lever arm, which is crucial to myosin's ability to transmit contractile force. The N47K and R58Q mutations have previously been shown to reduce actin filament velocity under load, stemming from a more compliant lever arm (Greenberg, 2010). In contrast, RLC phosphorylation was shown to impart stiffness to the myosin lever arm (Greenberg, 2009). We hypothesized that phosphorylation of the mutant HCM-RLC may mitigate distinct mutation-induced structural and functional abnormalities. In vitro motility assays were utilized to investigate the effects of RLC phosphorylation on the HCM-RLC mutant phenotype in the presence of an α-actinin frictional load. Porcine cardiac β-myosin was depleted of its native RLC and reconstituted with mutant or wild-type human RLC in phosphorylated or non-phosphorylated form. Consistent with previous findings, in the presence of load, myosin bearing the HCM mutations reduced actin sliding velocity compared to WT resulting in 31-41% reductions in force production. Myosin containing phosphorylated RLC (WT or mutant) increased sliding velocity and also restored mutant myosin force production to near WT unphosphorylated values. These results point to RLC phosphorylation as a general mechanism to increase force production of the individual myosin motor and as a potential target to ameliorate the HCM-induced phenotype at the molecular level.

Original languageEnglish (US)
Article number7007
Pages (from-to)14-21
Number of pages8
JournalArchives of Biochemistry and Biophysics
StatePublished - Jul 6 2015


  • Cardiac ventricular myosin
  • Hypertrophic cardiomyopathy
  • Load dependence
  • Regulatory light chain phosphorylation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology


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