title: Functions of myosin light chain-2 (MYL2) in cardiac muscle and disease.
abstract: Myosin light chain-2 (MYL2, also called MLC-2) is an ~19kDa sarcomeric protein that belongs to the EF-hand calcium binding protein superfamily and exists as three major isoforms encoded by three distinct genes in mammalian striated muscle. Each of the three different MLC-2 genes (MLC-2f; fast twitch skeletal isoform, MLC-2v; cardiac ventricular and slow twitch skeletal isoform, MLC-2a; cardiac atrial isoform) has a distinct developmental expression pattern in mammals. Genetic loss-of-function studies in mice demonstrated an essential role for cardiac isoforms of MLC-2, MLC-2v and MLC-2a, in cardiac contractile function during early embryogenesis. In the adult heart, MLC-2v function is regulated by phosphorylation, which displays a specific 1`expression pattern (high in epicardium and low in endocardium) across the heart. These data along with new data from computational models, genetic mouse models, and human studies have revealed a direct role for MLC-2v phosphorylation in cross-bridge cycling kinetics, calcium-dependent cardiac muscle contraction, cardiac torsion, cardiac function and various cardiac diseases. This review focuses on the regulatory functions of MLC-2 in the embryonic and adult heart, with an emphasis on phosphorylation-driven actions of MLC-2v in adult cardiac muscle, which provide new insights into mechanisms regulating myosin cycling kinetics and human cardiac diseases.
authors.affiliation: Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA. Electronic address: fasheikh@ucsd.edu.
authors.forename: Farah
authors.initials: F
authors.lastname: Sheikh
authors.affiliation: Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Lyon
authors.affiliation: Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA. Electronic address: juchen@ucsd.edu.
authors.forename: Ju
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D024722:Cardiac Myosins / Q000235:genetics* / Q000378:metabolism; D006321:Heart / Q000503:physiopathology*; D006352:Heart Ventricles / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D051379:Mice; D009135:Muscular Diseases / Q000235:genetics* / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D018994:Myosin Light Chains / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms
chemical_list: D018994:Myosin Light Chains; D020033:Protein Isoforms; C107184:myosin light chain 2; D024722:Cardiac Myosins
keywords: Cardiac disease; Cardiac function; Cardiac muscle; Cardiac torsion; Contraction; Heart; Myosin light chain kinase; Myosin light chain-2 (MYL2/MLC-2); Phosphorylation; Sarcomere; Ventricular myosin light chain-2