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. 2020 Dec;41(4):313-327.
doi: 10.1007/s10974-019-09517-x. Epub 2019 May 27.

Insights into myosin regulatory and essential light chains: a focus on their roles in cardiac and skeletal muscle function, development and disease

Yoel H Sitbon  1 , Sunil Yadav  1 , Katarzyna Kazmierczak  1 , Danuta Szczesna-Cordary  2
Affiliations

Insights into myosin regulatory and essential light chains: a focus on their roles in cardiac and skeletal muscle function, development and disease

Yoel H Sitbon et al. J Muscle Res Cell Motil. 2020 Dec.

Abstract

The activity of cardiac and skeletal muscles depends upon the ATP-coupled actin-myosin interactions to execute the power stroke and muscle contraction. The goal of this review article is to provide insight into the function of myosin II, the molecular motor of the heart and skeletal muscles, with a special focus on the role of myosin II light chain (MLC) components. Specifically, we focus on the involvement of myosin regulatory (RLC) and essential (ELC) light chains in striated muscle development, isoform appearance and their function in normal and diseased muscle. We review the consequences of isoform switching and knockout of specific MLC isoforms on cardiac and skeletal muscle function in various animal models. Finally, we discuss how dysregulation of specific RLC/ELC isoforms can lead to cardiac and skeletal muscle diseases and summarize the effects of most studied mutations leading to cardiac or skeletal myopathies.

Keywords: Development; Essential light chain; Function; Heart; Myopathy; Myosin; Regulatory light chain; Skeletal muscle; Transgenic mice.

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Figures

Figure 1.
Figure 1.
The myosin head (S1) derived from the atomic structure by Rayment et al., 1993. The heavy chain is shown in green, red, and blue to highlight functional domains. The essential light chain and regulatory light chain function to support the myosin neck region and are colored in yellow (ELC) and magenta (RLC) (pdb: 2MYS).
Figure 2.
Figure 2.
Domain organization of human isoforms of RLC (A) and ELC (B) proteins. Both light chains contain the EF-hand Ca2+ binding motifs (depicted with blue boxes) computed by UniProt (accession numbers listed in parentheses). Out of all EF-hand Ca2+ binding sites on RLC and ELC, only first EF-hand site on the RLC can bind Ca2+ and/or Mg2+. The N-terminal region of RLC contains phosphorylatable Serine(s) (Ser14/Ser15), targets of myosin light chain kinase (MLCK). The ELC contains two potential phosphorylation sites (T69 and S195), identified by proteomics. In addition to myosin heavy chain binding site, the N-terminus ELC contains additional actin binding site, allowing ELC to make molecular contacts with actin during contraction.
Figure 3.
Figure 3.
Developmental expression of myogenic factors and different isoforms of myosin light chains in skeletal (A) and cardiac (B) muscles of mice. E denotes embryonic day. Abbreviations of MLCs isoforms as in Fig. 2. Dashed lines indicate decreased transcript expression. For references, see paragraph II. Myogenesis of striated muscle components.
Figure 4.
Figure 4.
Effect of genetic manipulations in myosin light chains of cardiac and skeletal muscle observed in various animal models.
See this image and copyright information in PMC

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