Functional diversity among a family of human skeletal muscle myosin motors
Open accessAbstract
Human skeletal muscle fibers express five highly conserved type-II myosin heavy chain (MyHC) genes in distinct spatial and temporal patterns. In addition, the human genome contains an intact sixth gene, MyHC-IIb, which is thought under most circumstances not to be expressed. The physiological and biochemical properties of individual muscle fibers correlate with the predominantly expressed MyHC isoform, but a functional analysis of homogenous skeletal muscle myosin isoforms has not been possible. This is due to the difficulties of separating the multiple isoforms usually coexpressed in muscle fibers, as well as the lack of an expression system that produces active recombinant type II skeletal muscle myosin. In this study we describe a mammalian muscle cell expression system and the functional analysis of all six recombinant human type II skeletal muscle myosin isoforms. The diverse biochemical activities and actin-filament velocities of these myosins indicate that they likely have distinct functions in muscle. Our data also show that ATPase activity and motility are generally correlated for human skeletal muscle myosins. The exception, MyHC-IIb, encodes a protein that is high in ATPase activity but slow in motility; this is the first functional analysis of the protein from this gene. In addition, the developmental isoforms, hypothesized to have low ATPase activity, were indistinguishable from adult-fast MyHC-IIa and the specialized MyHC-Extraocular isoform, that was predicted to be the fastest of all six isoforms but was functionally similar to the slower isoforms.
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MyHC isoform expression directly affects muscle fiber-type contractile velocity via myosin ATPase activity, with relative velocities I < IIA < IIX < IIB.
“Functionally, MyHC isoform expression directly affects muscle fiber-type contractile velocity via myosin ATPase activity (74), with relative velocities of I < IIA < IIX < IIB (73, 74).”
From Sex-Based Differences in Skeletal Muscle Kinetics and Fiber-Type Composition (2015) · cites this paper as [74]
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“Given that the human MyHC-IIb gene is intact, highly conserved with the mouse MyHCIIb gene and capable of producing functional, enzymatically active myosin if expressed as recombinant protein [1,2,9,14], we sought to elucidate the molecular * Correspondence: leslie.”
BackgroundSelf-citation
- Authors
- Resnicow, D. I., Deacon, J. C., Warrick, H. M., Spudich, J. A., & Leinwand, L. A.
- Affiliations
- University of Colorado Boulder (US)
- Stanford Medicine (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-12-28
- Volume
- 107
- Issue
- 3
- Pages
- 1053-1058
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2824297
- OpenAlex
- W2046993766
- Cited by
- 116
- References
- 72
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 11 · 2023: 9 · 2022: 6 · 2021: 10 · 2020: 2 · 2019: 11 · 2018: 8 · 2017: 3 · 2016: 9 · 2015: 11 · 2014: 4 · 2013: 9 · 2012: 5
- FWCI
- 1.48
- Type
- journal article
- Language
- en
- Update notices
- correction (2010-05-13)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM033289, T32 GM65013, GM 29090, F32GM065013, GM33289, R01GM029090)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- skeletal muscle myosin, myosin heavy chain isoforms, ATPase activity, actin filament motility, muscle fiber type
- MeSH terms
- Adenosine Triphosphatases, Humans, Myosins, Muscle, Skeletal
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