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Functional role of myosin-binding protein H in thick filaments of developing vertebrate fast-twitch skeletal muscle.
Mead, Andrew F; Wood, Neil B; Nelson, Shane R; Palmer, Bradley M; Yang, Lin; Previs, Samantha Beck; Ploysangngam, Angela; Kennedy, Guy G; McAdow, Jennifer F; Tremble, Sarah M; Cipolla, Marilyn J; Ebert, Alicia M; Johnson, Aaron N; Gurnett, Christina A; Previs, Michael J; Warshaw, David M.
Afiliación
  • Mead AF; Department of Molecular Physiology and Biophysics, Larner College of Medicine, University of Vermont, Burlington, VT 05405.
  • Wood NB; Cardiovascular Research Institute, University of Vermont, Burlington, VT 05405.
  • Nelson SR; Department of Molecular Physiology and Biophysics, Larner College of Medicine, University of Vermont, Burlington, VT 05405.
  • Palmer BM; Department of Molecular Physiology and Biophysics, Larner College of Medicine, University of Vermont, Burlington, VT 05405.
  • Yang L; Cardiovascular Research Institute, University of Vermont, Burlington, VT 05405.
  • Previs SB; Department of Molecular Physiology and Biophysics, Larner College of Medicine, University of Vermont, Burlington, VT 05405.
  • Ploysangngam A; Cardiovascular Research Institute, University of Vermont, Burlington, VT 05405.
  • Kennedy GG; National Synchrotron Light Source II, Brookhaven National Laboratory, Upton, NY 11973.
  • McAdow JF; Department of Molecular Physiology and Biophysics, Larner College of Medicine, University of Vermont, Burlington, VT 05405.
  • Tremble SM; Cardiovascular Research Institute, University of Vermont, Burlington, VT 05405.
  • Cipolla MJ; Department of Molecular Physiology and Biophysics, Larner College of Medicine, University of Vermont, Burlington, VT 05405.
  • Ebert AM; Department of Molecular Physiology and Biophysics, Larner College of Medicine, University of Vermont, Burlington, VT 05405.
  • Johnson AN; Department of Neurlogical Sciences, Larner College of Medicine, University of Vermont, Burlington, VT 05405.
  • Gurnett CA; Department of Electrical and Biomedical Engineering, College of Engineering and Mathematical Sciences, University of Vermont, Burlington, VT 05405.
  • Previs MJ; Department of Electrical and Biomedical Engineering, College of Engineering and Mathematical Sciences, University of Vermont, Burlington, VT 05405.
  • Warshaw DM; Department of Neurology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
bioRxiv ; 2024 May 13.
Article en En | MEDLINE | ID: mdl-38798399
ABSTRACT
Myosin-binding protein H (MyBP-H) is a component of the vertebrate skeletal muscle sarcomere with sequence and domain homology to myosin-binding protein C (MyBP-C). Whereas skeletal muscle isoforms of MyBP-C (fMyBP-C, sMyBP-C) modulate muscle contractility via interactions with actin thin filaments and myosin motors within the muscle sarcomere "C-zone," MyBP-H has no known function. This is in part due to MyBP-H having limited expression in adult fast-twitch muscle and no known involvement in muscle disease. Quantitative proteomics reported here reveal MyBP-H is highly expressed in prenatal rat fast-twitch muscles and larval zebrafish, suggesting a conserved role in muscle development, and promoting studies to define its function. We take advantage of the genetic control of the zebrafish model and a combination of structural, functional, and biophysical techniques to interrogate the role of MyBP-H. Transgenic, FLAG-tagged MyBP-H or fMyBP-C both localize to the C-zones in larval myofibers, whereas genetic depletion of endogenous MyBP-H or fMyBP-C leads to increased accumulation of the other, suggesting competition for C-zone binding sites. Does MyBP-H modulate contractility from the C-zone? Globular domains critical to MyBP-C's modulatory functions are absent from MyBP-H, suggesting MyBP-H may be functionally silent. However, our results suggest an active role. Small angle x-ray diffraction of intact larval tails revealed MyBP-H contributes to the compression of the myofilament lattice accompanying stretch or contraction, while in vitro motility experiments indicate MyBP-H shares MyBP-C's capacity as a molecular "brake". These results provide new insights and raise questions about the role of the C-zone during muscle development.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos