Top-Down Proteomics Reveals Myofilament Proteoform Heterogeneity among Various Rat Skeletal Muscle Tissues
Open accessAbstract
Heterogeneity in skeletal muscle contraction time, peak power output, and resistance to fatigue, among others, is necessary to accommodate the wide range of functional demands imposed on the body. Underlying this functional heterogeneity are a myriad of differences in the myofilament protein isoform expression and post-translational modifications; yet, characterizing this heterogeneity remains challenging. Herein, we have utilized top-down liquid chromatography (LC)-mass spectrometry (MS)-based proteomics to characterize myofilament proteoform heterogeneity in seven rat skeletal muscle tissues including vastus lateralis, vastus medialis, vastus intermedius, rectus femoris, soleus, gastrocnemius, and plantaris. Top-down proteomics revealed that myofilament proteoforms varied greatly across the seven different rat skeletal muscle tissues. Subsequently, we quantified and characterized myofilament proteoforms using online LC-MS. We have comprehensively characterized the fast and slow skeletal troponin I isoforms, which demonstrates the ability of top-down MS to decipher isoforms with high sequence homology. Taken together, we have shown that top-down proteomics can be used as a robust and high-throughput method to characterize the molecular heterogeneity of myofilament proteoforms from various skeletal muscle tissues.
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Skeletal muscle is highly heterogeneous in its myofilament proteoforms.
“Quantitative top-down proteomics discovered that there were distinct differences in the myofilament proteoforms found across the seven various rat skeletal muscle tissues, which demonstrates the highly heterogeneous nature of skeletal muscle (Figure 6) [154].”
From Top-down proteomics: challenges, innovations, and applications in basic and clinical research (2020) · cites this paper as [154]
Distinct differences in myofilament proteoforms were found across seven various rat skeletal muscle tissues.
“Quantitative top-down proteomics discovered that there were distinct differences in the myofilament proteoforms found across the seven various rat skeletal muscle tissues, which demonstrates the highly heterogeneous nature of skeletal muscle (Figure 6) [154].”
From Top-down proteomics: challenges, innovations, and applications in basic and clinical research (2020) · cites this paper as [154]
Melby et al. performed top-down proteomics on seven different rat skeletal muscle tissues: vastus lateralis, vastus medialis, vastus intermedius, rectus femoris, soleus, gastrocnemius, and plantaris.
“Melby et al. expanded upon this study by performing top-down proteomics on seven different rat skeletal muscle tissues: vastus lateralis (VL), vastus medialis (VM), vastus intermedius (VI), rectus femoris (RF), soleus (SOL), gastrocnemius (GAS), and plantaris (PLN) [154].”
From Top-down proteomics: challenges, innovations, and applications in basic and clinical research (2020) · cites this paper as [154]
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- Authors
- Melby, J. A., Jin, Y., Lin, Z., Tucholski, T., Wu, Z., Gregorich, Z. R., Diffee, G. M., & Ge, Y.
- Affiliations
- University of Wisconsin–Madison (US)
- Corresponding author
- Ge, Ying
- ORCID
- Venue
- Journal of Proteome Research
- Publisher
- American Chemical Society (ACS)
- Published
- 2019-10-24
- Volume
- 19
- Issue
- 1
- Pages
- 446-454
- ISSN
- 1535-3893 (ISSN-L)
- 1535-3907
- PMC
- PMC7487979
- OpenAlex
- W2982218778
- Cited by
- 20
- References
- 51
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 1 · 2021: 5 · 2020: 4
- FWCI
- 1.00
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- Locations
- Journal of Proteome Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL096971, HL109810)
- National Institute of General Medical Sciences (GM117058, GM125085)
- NIH Instrumentation Grant (S10OD018475)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- skeletal muscle, top-down proteomics, troponin I isoforms, post-translational modification, rat skeletal muscle, Vastu, soleus muscle, gastrocnemius, plantaris, rectus femoris, muscle contraction time, fatigue resistance
- MeSH terms
- Animals, Chromatography, Liquid, Electrophoresis, Polyacrylamide Gel, Male, Muscle Proteins, Myofibrils, Rats, Inbred F344, Muscle, Skeletal, Troponin T, Proteomics, Tandem Mass Spectrometry
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