Myosin light chain phosphorylation, novel targets to repair a broken heart?

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This editorial refers to ‘Acute heart failure with cardiomyocyte atrophy induced in adult mice by ablation of cardiac myosin light chain kinase’, by M.T. Massengill et al ., pp. 34–43. This editorial refers to ‘Essential light chain S195 phosphorylation is required for cardiac adaptation under physical stress’, by L.-M. Scheid et al ., pp. 44–55. The process of ATP-dependent cyclic attachments and detachments of the myosin cross-bridges to actin-containing thin filaments forms the basis of muscle contraction.1 As such, the myosin cross-bridge is the molecular motor of the heart. It binds ATP and actin and myosin's lever arm region, supported by the regulatory light chain (RLC) and essential light chain (ELC) ( Figure 1A and B ), amplifies small conformational changes generated in the motor domain into the large movements needed to produce force and sarcomere shortening.2 As an EF-hand Ca2+-binding protein, the RLC contains a Ca2+–Mg2+ binding site that can be occupied by either Ca2+ or Mg2+, and a Ser15 phosphorylation site, a target for cardiac myosin light chain kinase (cMLCK) encoded by the MYLK3 gene. The ELC is also an EF-hand-like protein; however, cardiac muscle ELC has developmentally lost its ability to bind calcium. Proteomic analysis by the Van Eyk's group revealed that residue Ser195 of ELC can be phosphorylated in pharmacologically preconditioned cardiomyocytes, although no specific kinase responsible for Ser195-ELC phosphorylation has yet been identified.3 Two new articles, published in this issue of Cardiovascular Research by Massengill et al. 4 and Scheid et al. ,5 focus on the functional impacts of myosin RLC and ELC phosphorylation on heart function in a mouse model of …