Muscle Lim protein interacts with cofilin 2 and regulates F-actin dynamics in cardiac and skeletal muscle

Vasiliki Papalouka, Demetrios A. Arvanitis, Elizabeth Vafiadaki, Manolis Mavroidis, Stavroula A. Papadodima, Chara A. Spiliopoulou, Dimitrios T. Kremastinos, Evangelia G. Kranias, Despina Sanoudou

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    Abstract

    The muscle LIM protein (MLP) and cofilin 2 (CFL2) are important regulators of striated myocyte function. Mutations in the corresponding genes have been directly associated with severe human cardiac and skeletal myopathies, and aberrant expression patterns have often been observed in affected muscles. Herein, we have investigated whether MLP and CFL2 are involved in common molecular mechanisms, which would promote our understanding of disease pathogenesis. We have shown for the first time, using a range of biochemical and immunohistochemical methods, that MLP binds directly to CFL2 in human cardiac and skeletal muscles. The interaction involves the inter-LIM domain, amino acids 94 to 105, of MLP and the amino-terminal domain, amino acids 1 to 105, of CFL2, which includes part of the actin depolymerization domain. The MLP/CFL2 complex is stronger in moderately acidic (pH 6.8) environments and upon CFL2 phosphorylation, while it is independent of Ca2+ levels. This interaction has direct implications in actin cytoskeleton dynamics in regulating CFL2-dependent F-actin depolymerization, with maximal depolymerization enhancement at an MLP/CFL2 molecular ratio of 2:1. Deregulation of this interaction by intracellular pH variations, CFL2 phosphorylation, MLP or CFL2 gene mutations, or expression changes, as observed in a range of cardiac and skeletal myopathies, could impair F-actin depolymerization, leading to sarcomere dysfunction and disease.

    Original languageEnglish
    Pages (from-to)6046-6058
    Number of pages13
    JournalMolecular and Cellular Biology
    Volume29
    Issue number22
    DOIs
    Publication statusPublished - 1 Nov 2009

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    ASJC Scopus subject areas

    • Molecular Biology
    • Cell Biology

    Cite this

    Papalouka, V., Arvanitis, D. A., Vafiadaki, E., Mavroidis, M., Papadodima, S. A., Spiliopoulou, C. A., Kremastinos, D. T., Kranias, E. G., & Sanoudou, D. (2009). Muscle Lim protein interacts with cofilin 2 and regulates F-actin dynamics in cardiac and skeletal muscle. Molecular and Cellular Biology, 29(22), 6046-6058. https://doi.org/10.1128/MCB.00654-09