Journal of Muscle Research and Cell Motility

, Volume 36, Issue 6, pp 433–445 | Cite as

Molecular mechanisms of cardiomyopathy phenotypes associated with myosin light chain mutations

  • Wenrui Huang
  • Danuta Szczesna-Cordary
Review Article


We discuss here the potential mechanisms of action associated with hypertrophic (HCM) or dilated (DCM) cardiomyopathy causing mutations in the myosin regulatory (RLC) and essential (ELC) light chains. Specifically, we focus on four HCM mutations: RLC-A13T, RLC-K104E, ELC-A57G and ELC-M173V, and one DCM RLC-D94A mutation shown by population studies to cause different cardiomyopathy phenotypes in humans. Our studies indicate that RLC and ELC mutations lead to heart disease through different mechanisms with RLC mutations triggering alterations of the secondary structure of the RLC which further affect the structure and function of the lever arm domain and impose changes in the cross bridge cycling rates and myosin force generation ability. The ELC mutations exert their detrimental effects through changes in the interaction of the N-terminus of ELC with actin altering the cross talk between the thick and thin filaments and ultimately resulting in an altered force-pCa relationship. We also discuss the effect of mutations on myosin light chain phosphorylation. Exogenous myosin light chain phosphorylation and/or pseudo-phosphorylation were explored as potential rescue tools to treat hypertrophy-related cardiac phenotypes.


Myosin light chains Mutation Cardiomyopathy Structure Function Phosphorylation 



Alanine-to-threonine mutation in myosin RLC


Alanine-to-glycine mutation in myosin ELC


Atrial natriuretic peptide


Brain natriuretic peptide




Circular dichroism


Cardiac output


Aspartic acid-to-alanine mutation in myosin RLC


Aspartic acid-to-valine mutation in myosin RLC


Dilated cardiomyopathy

E/A ratio

Doppler transmitral blood velocities, early (E)/late (A) diastolic




Ejection fraction


Essential light chain of myosin (MYL3 gene)


Hypertrophic cardiomyopathy


Interfilament lattice spacing


Inter-ventricular septum


Hematoxylin and eosin


Heart failure


Lysine-to-glutamic acid mutation in myosin RLC


Left ventricle


Methionine-to-valine mutation in myosin ELC


Myosin heavy chain


Myosin light chain


Myosin light chain kinase


Myosin binding protein-C




Pressure volume


Arginine-to-glutamine mutation in myosin RLC


Regulatory light chain of myosin (MYL2 gene)


Serine-to-aspartic acid mutation to mimic phosphorylation


Sudden cardiac death


Sarcoplasmic reticulum


Stroke work


Stroke volume











The authors thank Michelle Jones for critical reading of the manuscript. This work was supported in part by grants from the National Institutes of Health HL108343 and HL123255 (D.S-C.); and the American Heart Association 12PRE12030412 (W.H.). The content is solely the responsibility of the authors and does not necessarily reflect the official views of the National Center for Research Resources or the NIH.


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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of Molecular and Cellular PharmacologyUniversity of Miami Miller School of MedicineMiamiUSA

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