Myosin Light Chain 2 Into the Mainstream of Cardiac Development and Contractility

Abstract

See related article, pages 323–331 Myocardium exhibits a remarkably broad dynamic range of function that is normally well matched to the circulatory load on the heart. Regulation of cardiac contraction is a multifaceted process that is well understood in terms of the activating role of Ca2+ but much less well in terms of modulation by thick filament accessory proteins and by post-translational modification of thick and thin filament proteins.1,2 In this issue of Circulation Research , an elegant study by Fishman and colleagues3 dramatically reinforces the idea that the light chain 2 subunit of myosin (MLC-2) is critically important in myocardium by showing that MLC-2 loss because of mutation abolishes myofibrillar assembly in zebrafish, resulting in embryonic lethality. Earlier work had shown that mutations in MLC-2 account for some cases of hypertrophic cardiomyopathy4 and that phosphorylation of MLC-2 contributes to cardiac pump function,5 but now it is evident that MLC-2 has an obligatory role in development. Cardiac isoforms of myosin II comprise the motor of myocardial contraction and like all members of this family are composed of 6 subunits6: 2 myosin heavy chains of &200 kDa molecular weight, 2 so-called essential light chains (or light chain 1) of &17 kDa, and 2 regulatory light chains (or light chain 2) of >20 kDa. Subfragment 1 of the heavy chain (Figure) comprises the business end of the motor, containing both the nucleotide and actin-binding sites, whereas the light chains wrap around the rod-like extension of subfragment 1 and are believed to function (minimally) as mechanical stabilizers of this part of myosin during force generation and mechanical work performance. This motor is impressive for its efficiency and its …