title: X-ray diffraction evidence for myosin-troponin connections and tropomyosin movement during stretch activation of insect flight muscle.
abstract: Stretch activation is important in the mechanical properties of vertebrate cardiac muscle and essential to the flight muscles of most insects. Despite decades of investigation, the underlying molecular mechanism of stretch activation is unknown. We investigated the role of recently observed connections between myosin and troponin, called "troponin bridges," by analyzing real-time X-ray diffraction "movies" from sinusoidally stretch-activated Lethocerus muscles. Observed changes in X-ray reflections arising from myosin heads, actin filaments, troponin, and tropomyosin were consistent with the hypothesis that troponin bridges are the key agent of mechanical signal transduction. The time-resolved sequence of molecular changes suggests a mechanism for stretch activation, in which troponin bridges mechanically tug tropomyosin aside to relieve tropomyosin's steric blocking of myosin-actin binding. This enables subsequent force production, with cross-bridge targeting further enhanced by stretch-induced lattice compression and thick-filament twisting. Similar linkages may operate in other muscle systems, such as mammalian cardiac muscle, where stretch activation is thought to aid in cardiac ejection.
authors.affiliation: Department of Cell Biology, Box 3011, Duke University, Durham, NC 27710, USA. rjpe@cellbio.duke.edu
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Perz-Edwards
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Irving
authors.forename: Bruce A J
authors.initials: BA
authors.lastname: Baumann
authors.forename: David
authors.initials: D
authors.lastname: Gore
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Hutchinson
authors.forename: Uroš
authors.initials: U
authors.lastname: Kržič
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Porter
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Ward
authors.forename: Michael K
authors.initials: MK
authors.lastname: Reedy
mesh_terms: D000199:Actins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D001696:Biomechanical Phenomena; D002118:Calcium / Q000378:metabolism; D005426:Flight, Animal / Q000502:physiology*; D020062:Heteroptera / Q000737:chemistry* / Q000502:physiology; D008954:Models, Biological; D008958:Models, Molecular; D009132:Muscles / Q000737:chemistry* / Q000502:physiology / Q000648:ultrastructure; D015398:Signal Transduction / Q000502:physiology*; D014335:Tropomyosin / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D014961:X-Ray Diffraction
chemical_list: D000199:Actins; D014335:Tropomyosin; D002118:Calcium