Pointed-end capping by tropomodulin modulates actomyosin crossbridge formation in skeletal muscle fibers.
In skeletal muscle, thick and thin filaments are arranged in a myofibrillar lattice. Tropomodulin 1 (Tmod1) is a pointed-end capping and tropomyosin-binding protein that controls thin-filament assembly, stability, and lengths. It remains unknown whether Tmods have other functional roles, such as regulating muscle contractility. To investigate this, we recorded and analyzed the mechanical properties and X-ray diffraction patterns of single membrane-permeabilized skeletal muscle fibers from mice lacking Tmod1. Results show that absence of Tmod1 and its replacement by Tmod3 and Tmod4 may impair initial tropomyosin movement over actin subunits during thin-filament activation, thus reducing both the fraction of actomyosin crossbridges in the strongly bound state (-29%) and fiber force-generating capacity (-31%). Therefore, Tmods are novel regulators of actomyosin crossbridge formation and muscle contractility, and future investigations and models of skeletal muscle force production must incorporate Tmods.
1Centre of Human and Aerospace Physiological Sciences, School of Biomedical Sciences, King's College London, Rm. 3.3, Shepherd's House, Guy's Campus, London SE1 1UL, UK. julien.ochala@kcl.ac.uk.
Julien
J
Ochala
David S
DS
Gokhin
Hiroyuki
H
Iwamoto
Velia M
VM
Fowler
D000205:Actomyosin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D051379:Mice; D018345:Mice, Knockout; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D051348:Tropomodulin / Q000235:genetics / Q000378:metabolism*; D014961:X-Ray Diffraction
D051348:Tropomodulin; D000205:Actomyosin
thin-filament activation; tropomyosin