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      Lattice arrangement of myosin filaments correlates with fiber type in rat skeletal muscle

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          Abstract

          Ma et al. studied the 3-D arrangement of thick filaments in skeletal muscle by x-ray diffraction and electron microscopy and found a correlation between thick filament lattice type (simple or superlattice) and fiber type (fast/slow). This suggests that lattice organization contributes to muscle functional properties.

          Abstract

          The thick (myosin-containing) filaments of vertebrate skeletal muscle are arranged in a hexagonal lattice, interleaved with an array of thin (actin-containing) filaments with which they interact to produce contraction. X-ray diffraction and EM have shown that there are two types of thick filament lattice. In the simple lattice, all filaments have the same orientation about their long axis, while in the superlattice, nearest neighbors have rotations differing by 0° or 60°. Tetrapods (amphibians, reptiles, birds, and mammals) typically have only a superlattice, while the simple lattice is confined to fish. We have performed x-ray diffraction and electron microscopy of the soleus (SOL) and extensor digitorum longus (EDL) muscles of the rat and found that while the EDL has a superlattice as expected, the SOL has a simple lattice. The EDL and SOL of the rat are unusual in being essentially pure fast and slow muscles, respectively. The mixed fiber content of most tetrapod muscles and/or lattice disorder may explain why the simple lattice has not been apparent in these vertebrates before. This is supported by only weak simple lattice diffraction in the x-ray pattern of mouse SOL, which has a greater mix of fiber types than rat SOL. We conclude that the simple lattice might be common in tetrapods. The correlation between fiber type and filament lattice arrangement suggests that the lattice arrangement may contribute to the functional properties of a muscle.

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          Force generation by skeletal muscle is controlled by mechanosensing in myosin filaments.

          Contraction of both skeletal muscle and the heart is thought to be controlled by a calcium-dependent structural change in the actin-containing thin filaments, which permits the binding of myosin motors from the neighbouring thick filaments to drive filament sliding. Here we show by synchrotron small-angle X-ray diffraction of frog (Rana temporaria) single skeletal muscle cells that, although the well-known thin-filament mechanism is sufficient for regulation of muscle shortening against low load, force generation against high load requires a second permissive step linked to a change in the structure of the thick filament. The resting (switched 'OFF') structure of the thick filament is characterized by helical tracks of myosin motors on the filament surface and a short backbone periodicity. This OFF structure is almost completely preserved during low-load shortening, which is driven by a small fraction of constitutively active (switched 'ON') myosin motors outside thick-filament control. At higher load, these motors generate sufficient thick-filament stress to trigger the transition to its long-periodicity ON structure, unlocking the major population of motors required for high-load contraction. This concept of the thick filament as a regulatory mechanosensor provides a novel explanation for the dynamic and energetic properties of skeletal muscle. A similar mechanism probably operates in the heart.
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            The low-angle x-ray diagram of vertebrate striated muscle and its behaviour during contraction and rigor.

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              ELECTRON MICROSCOPE STUDIES ON THE STRUCTURE OF NATURAL AND SYNTHETIC PROTEIN FILAMENTS FROM STRIATED MUSCLE.

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                Author and article information

                Journal
                J Gen Physiol
                J. Gen. Physiol
                jgp
                jgp
                The Journal of General Physiology
                Rockefeller University Press
                0022-1295
                1540-7748
                02 December 2019
                7 November 2019
                : 151
                : 12
                : 1404-1412
                Affiliations
                [1 ]Department of Biological Sciences, Illinois Institute of Technology, Chicago, IL
                [2 ]Division of Cell Biology and Imaging, Department of Radiology, University of Massachusetts Medical School, Worcester, MA
                Author notes
                Correspondence to Roger Craig: roger.craig@ 123456umassmed.edu
                [*]

                W. Ma, K.H. Lee, and S. Yang contributed equally to this study.

                A non–peer-reviewed preprint version of this manuscript is available at https://www.biorxiv.org/content/10.1101/720300v1.

                Author information
                https://orcid.org/0000-0003-1423-8952
                https://orcid.org/0000-0003-4848-3323
                https://orcid.org/0000-0002-9707-5409
                Article
                201912460
                10.1085/jgp.201912460
                6888752
                31699797
                e57ae2b2-d6a6-41cf-9c3f-d82e21608bb5
                © 2019 Ma et al.

                This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).

                History
                : 30 July 2019
                : 09 October 2019
                Page count
                Pages: 9
                Funding
                Funded by: National Institutes of Health, DOI https://doi.org/10.13039/100000002;
                Award ID: AR072036
                Award ID: AR067279
                Award ID: HL139883
                Funded by: U.S. Department of Energy, DOI https://doi.org/10.13039/100000015;
                Funded by: Argonne National Laboratory, DOI https://doi.org/10.13039/10.13039/100006224;
                Award ID: DE-AC02-06CH11357
                Funded by: National Institute of General Medical Sciences, DOI https://doi.org/10.13039/100000057;
                Award ID: P41 GM103622
                Funded by: National Institute of General Medical Sciences, DOI https://doi.org/10.13039/100000057;
                Award ID: 1S10OD018090-01
                Funded by: National Institutes of Health, DOI https://doi.org/10.13039/100000002;
                Award ID: 1S10ODO21580-01
                Categories
                Research Articles
                Research Article
                501
                505

                Anatomy & Physiology
                Anatomy & Physiology

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