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Regulation of myosin light-chain phosphorylation and its roles in cardiovascular physiology and pathophysiology

Hypertension Research volume 45, pages 40–52 (2022)Cite this article

Abstract

The regulation of muscle contraction is a critical function in the cardiovascular system, and abnormalities may be life-threatening or cause illness. The common basic mechanism in muscle contraction is the interaction between the protein filaments myosin and actin. Although this interaction is primarily regulated by intracellular Ca2+, the primary targets and intracellular signaling pathways differ in vascular smooth muscle and cardiac muscle. Phosphorylation of the myosin regulatory light chain (RLC) is a primary molecular switch for smooth muscle contraction. The equilibrium between phosphorylated and unphosphorylated RLC is dynamically achieved through two enzymes, myosin light chain kinase, a Ca2+-dependent enzyme, and myosin phosphatase, which modifies the Ca2+ sensitivity of contractions. In cardiac muscle, the primary target protein for Ca2+ is troponin C on thin filaments; however, RLC phosphorylation also plays a modulatory role in contraction. This review summarizes recent advances in our understanding of the regulation, physiological function, and pathophysiological involvement of RLC phosphorylation in smooth and cardiac muscles.

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Acknowledgements

We are grateful to the members of the Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, for the execution and support of our research. We also thank Dr. David J Hartshorne at the University of Arizona, Dr. Ferenc Erdődi at the University of Debrecen, and Dr. Kozo Kaibuchi at Nagoya University for their collaboration.

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  1. Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Japan

    Masaaki Ito, Ryuji Okamoto, Hiromasa Ito, Ye Zhe & Kaoru Dohi

  2. Department of Clinical Training and Career Support, Mie University Hospital, Tsu, Japan

    Masaaki Ito & Ryuji Okamoto

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  1. Masaaki Ito
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M.I., R.O., H.I., Y.Z. and K.O. wrote the manuscript.

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Ito, M., Okamoto, R., Ito, H. et al. Regulation of myosin light-chain phosphorylation and its roles in cardiovascular physiology and pathophysiology. Hypertens Res 45, 40–52 (2022). https://doi.org/10.1038/s41440-021-00733-y

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