Regulation of myofilament force and loaded shortening by skeletal myosin binding protein C

Robinett, Joel C.; Hanft, Laurin M.; Geist, Janelle; Kontrogianni‐Konstantopoulos, Aikaterini; McDonald, Kerry S.

doi:10.1085/jgp.201812200

Cited by 40 publications

(60 citation statements)

References 65 publications

(109 reference statements)

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“…3 and 5). This thin filament slowing upon entering the C-zone has recently been confirmed during fiber shortening in skinned rat SOL skeletal muscle fibers (19). Thin filament slowing appears to be inherent to the N termini of all slow-and fast-type MyBP-C fragments characterized in the motility assay, with 2 exceptions (Fig.…”

Section: Discussionmentioning

confidence: 55%

“…As such, the differential expressions of slow-and fast-type MyBP-C isoforms may enable the muscle to fine-tune its mechanical performance, depending on the muscle's physiological demands, such as exercise and potentially during development and aging. It is worth noting that, at least, the slow-type MyBP-C is posttranslationally modified by phosphorylation of its N-terminal domains (19,(45)(46)(47). Therefore, N-terminal phosphorylation of the slow-type MyBP-C may provide additional means of regulating its modulatory capacity both normally, under acute physiological stress, and abnormally, due to genetic mutations in MyBP-C that lead to skeletal myopathies (19,(45)(46)(47).…”

Section: Discussionmentioning

confidence: 99%

“…Specifically, N-terminal fragment binding to the thin filament can sensitize the thin filament to calcium by shifting the position of tropomyosin out of the "blocked" state to facilitate myosin binding to actin (18). In addition, MyBP-C can act as a "brake" to reduce sarcomere shortening (19) and thin filament sliding velocity (17,18) through its interaction with either the thin filament and/or myosin head region. Although extremely informative, the in vitro N-terminal fragment studies described above were performed with contractile proteins isolated from heterologous species or muscle tissue, creating nonnative simplified contractile model systems.…”

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confidence: 99%

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Skeletal MyBP-C isoforms tune the molecular contractility of divergent skeletal muscle systems

Nelson

Rahmanseresht

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Skeletal muscle myosin-binding protein C (MyBP-C) is a myosin thick filament-associated protein, localized through its C terminus to distinct regions (C-zones) of the sarcomere. MyBP-C modulates muscle contractility, presumably through its N terminus extending from the thick filament and interacting with either the myosin head region and/or the actin thin filament. Two isoforms of MyBP-C (fast- and slow-type) are expressed in a muscle type-specific manner. Are the expression, localization, and Ca2+-dependent modulatory capacities of these isoforms different in fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus (SOL) muscles derived from Sprague–Dawley rats? By mass spectrometry, 4 MyBP-C isoforms (1 fast-type MyBP-C and 3 N-terminally spliced slow-type MyBP-C) were expressed in EDL, but only the 3 slow-type MyBP-C isoforms in SOL. Using EDL and SOL native thick filaments in which the MyBP-C stoichiometry and localization are preserved, native thin filament sliding over these thick filaments showed that, only in the C-zone, MyBP-C Ca2+ sensitizes the thin filament and slows thin filament velocity. These modulatory properties depended on MyBP-C’s N terminus as N-terminal proteolysis attenuated MyBP-C’s functional capacities. To determine each MyBP-C isoform’s contribution to thin filament Ca2+ sensitization and slowing in the C-zone, we used a combination of in vitro motility assays using expressed recombinant N-terminal fragments and in silico mechanistic modeling. Our results suggest that each skeletal MyBP-C isoform’s N terminus is functionally distinct and has modulatory capacities that depend on the muscle type in which they are expressed, providing the potential for molecular tuning of skeletal muscle performance through differential MyBP-C expression.

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Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Skeletal MyBP-C isoforms tune the molecular contractility of divergent skeletal muscle systems

Nelson

Rahmanseresht

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…Different fibre types may have different titin isoforms, which give them different elastic properties [31]. Myosin filaments are also labelled in the central third of each bridge region by C-protein (Myosin Binding Protein-C; MyBP-C; Figure 4) which can have structural and regulatory roles [34,35,36].…”

Section: Striated Muscle Sarcomeres and The Contractile Mechanismmentioning

confidence: 99%

Special Issue: The Actin-Myosin Interaction in Muscle: Background and Overview

Squire

2019

IJMS

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Muscular contraction is a fundamental phenomenon in all animals; without it life as we know it would be impossible. The basic mechanism in muscle, including heart muscle, involves the interaction of the protein filaments myosin and actin. Motility in all cells is also partly based on similar interactions of actin filaments with non-muscle myosins. Early studies of muscle contraction have informed later studies of these cellular actin-myosin systems. In muscles, projections on the myosin filaments, the so-called myosin heads or cross-bridges, interact with the nearby actin filaments and, in a mechanism powered by ATP-hydrolysis, they move the actin filaments past them in a kind of cyclic rowing action to produce the macroscopic muscular movements of which we are all aware. In this special issue the papers and reviews address different aspects of the actin-myosin interaction in muscle as studied by a plethora of complementary techniques. The present overview provides a brief and elementary introduction to muscle structure and function and the techniques used to study it. It goes on to give more detailed descriptions of what is known about muscle components and the cross-bridge cycle using structural biology techniques, particularly protein crystallography, electron microscopy and X-ray diffraction. It then has a quick look at muscle mechanics and it summarises what can be learnt about how muscle works based on the other studies covered in the different papers in the special issue. A picture emerges of the main molecular steps involved in the force-producing process; steps that are also likely to be seen in non-muscle myosin interactions with cellular actin filaments. Finally, the remarkable advances made in studying the effects of mutations in the contractile assembly in causing specific muscle diseases, particularly those in heart muscle, are outlined and discussed.

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“…The different forms of MyBP-C in different fiber types might link filaments differently, contributing to formation of the two types of lattice. If so, this would represent a novel function of MyBP-C, a protein whose role in skeletal muscle is not yet well understood (Wang et al, 2018;Li et al, 2019;Robinett et al, 2019). MyBP-C is in fact long enough to directly link thick filaments, which could more directly influence lattice formation, although there is so far no evidence that such connections exist in the myofibril (Luther et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

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

Lee

Yang

et al. 2019

Journal of General Physiology

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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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Regulation of myofilament force and loaded shortening by skeletal myosin binding protein C

Cited by 40 publications

References 65 publications

Skeletal MyBP-C isoforms tune the molecular contractility of divergent skeletal muscle systems

Skeletal MyBP-C isoforms tune the molecular contractility of divergent skeletal muscle systems

Special Issue: The Actin-Myosin Interaction in Muscle: Background and Overview

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

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