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Disease causing mutations of troponin alter regulated actin state distributions

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Abstract

Striated muscle contraction is regulated primarily through the action of tropomyosin and troponin that are bound to actin. Activation requires Ca2+ binding to troponin and/or binding of high affinity myosin complexes to actin. Mutations within components of the regulatory complex may lead to familial cardiomyopathies and myopathies. In several cases examined, either physiological or pathological changes in troponin alter the distribution among states of actin–tropomyosin–troponin that differ in their abilities to stimulate myosin ATPase activity. These observations open possibilities for managing disorders of the troponin complex. Furthermore, analyses of mutant forms of troponin give insights into the regulation of striated muscle contraction.

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Abbreviations

S1:

Myosin subfragment 1

NEM-S1:

S1 modified with N-ethylmaleimide

Regulated actin:

The complex of actin–tropomyosin and troponin

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Brody School of Medicine at East Carolina University, Greenville, NC, USA

    Joseph M. Chalovich

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  1. Joseph M. Chalovich
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Correspondence to Joseph M. Chalovich.

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I last spoke with Michael Barany in 2008 at the University of Illinois School of Medicine. He encouraged me to write a review on the topic of a seminar that I had just given in the Department of Physiology & Biophysics. This brief review honors that request.

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Chalovich, J.M. Disease causing mutations of troponin alter regulated actin state distributions. J Muscle Res Cell Motil 33, 493–499 (2012). https://doi.org/10.1007/s10974-012-9305-x

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  • DOI: https://doi.org/10.1007/s10974-012-9305-x

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