Fast myosin binding protein C knockout in skeletal muscle alters length-dependent activation and myofilament structure.

Autor: Hessel AL; Institute of Physiology II, University of Muenster, Muenster, Germany. anthony.hessel@uni-muenster.de., Kuehn MN; Institute of Physiology II, University of Muenster, Muenster, Germany., Han SW; Institute of Physiology II, University of Muenster, Muenster, Germany., Ma W; BioCAT, Department of Biology, Illinois Institute of Technology, Chicago, USA., Irving TC; BioCAT, Department of Biology, Illinois Institute of Technology, Chicago, USA., Momb BA; Department of Kinesiology, University of Massachusetts-Amherst, Amherst, MA, USA., Song T; Center for Cardiovascular Research, Division of Cardiovascular Health and Disease, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA., Sadayappan S; Center for Cardiovascular Research, Division of Cardiovascular Health and Disease, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA., Linke WA; Institute of Physiology II, University of Muenster, Muenster, Germany., Palmer BM; Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, VT, USA. Bradley.palmer@uvm.edu.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2024 May 27; Vol. 7 (1), pp. 648. Date of Electronic Publication: 2024 May 27.
DOI: 10.1038/s42003-024-06265-8
Abstrakt: In striated muscle, the sarcomeric protein myosin-binding protein-C (MyBP-C) is bound to the myosin thick filament and is predicted to stabilize myosin heads in a docked position against the thick filament, which limits crossbridge formation. Here, we use the homozygous Mybpc2 knockout (C2 -/- ) mouse line to remove the fast-isoform MyBP-C from fast skeletal muscle and then conduct mechanical functional studies in parallel with small-angle X-ray diffraction to evaluate the myofilament structure. We report that C2 -/- fibers present deficits in force production and calcium sensitivity. Structurally, passive C2 -/- fibers present altered sarcomere length-independent and -dependent regulation of myosin head conformations, with a shift of myosin heads towards actin. At shorter sarcomere lengths, the thin filament is axially extended in C2 -/- , which we hypothesize is due to increased numbers of low-level crossbridges. These findings provide testable mechanisms to explain the etiology of debilitating diseases associated with MyBP-C.
(© 2024. The Author(s).)
Databáze: MEDLINE
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