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Cardiac Cytoarchitecture pp 71–88Cite as

Dynamics of Actin in the Heart: Defining Thin Filament Length

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Abstract

Cardiac sarcomeres are composed of overlapping actin-thin filaments and myosin-thick filaments. Efficient muscle contraction is dependent on the proper overlap of thick and thin filaments; therefore filament lengths are tightly regulated. The actin-thin filament is a polar structure with a distinct barbed end (at the Z-disc) and pointed end (at the M-line). Capping proteins bind to and regulate thin filament lengths at the ends of the filament. For instance, tropomodulin 1 (Tmod1) caps (blocks the incorporation and dissociation of G-actin) the pointed end of the thin filament, while CapZ caps the barbed end. Leiomodin 2 (Lmod2), a close family member of Tmod1, also binds to the pointed end but it elongates thin filaments. Lmod2 and Tmod1 compete to bind to the pointed end, which fine tunes thin filament length. While capping/elongation proteins play a critical role in length regulation, other proteins have been proposed to contribute. For instance, tropomyosin plays a vital role in stabilizing the thin filament. In addition, cyclase-associated protein 2 (CAP2) has been proposed to regulate thin filament length by severing filamentous actin and sequestering globular actin. Actin-monomer-binding proteins may also work in conjunction with capping proteins to regulate length. Due to the critical role these proteins play in maintaining lengths, it is not surprising that alterations or mutations in many of these proteins result in the development of human cardiomyopathies. Current research is focused on dissecting the role that alterations in thin filament length have in both normal heart function and the development of disease.

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Acknowledgments

This work was funded by NIH grant HL123078 (C.C.G) and a predoctoral fellowship from the American Heart Association Western States Affiliate (13PRE14340043 to C.A.H).

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  1. Department of Cellular and Molecular Medicine, University of Arizona, 1656 East Mabel, Tucson, AZ, 85724, USA

    Christine A. Henderson & Carol C. Gregorio

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Correspondence to Carol C. Gregorio .

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  1. Randall Div. of Cell and Mol. Biophysics and Cardiovascular Division Guy’s Campus, Faculty of Life Sciences and Medicine King’s College London, London, United Kingdom

    Elisabeth Ehler

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Henderson, C.A., Gregorio, C.C. (2015). Dynamics of Actin in the Heart: Defining Thin Filament Length. In: Ehler, E. (eds) Cardiac Cytoarchitecture. Springer, Cham. https://doi.org/10.1007/978-3-319-15263-9_4

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