title: Roles for cardiac MyBP-C in maintaining myofilament lattice rigidity and prolonging myosin cross-bridge lifetime.
abstract: We investigated the influence of cardiac myosin binding protein-C (cMyBP-C) and its constitutively unphosphorylated status on the radial and longitudinal stiffnesses of the myofilament lattice in chemically skinned myocardial strips of the following mouse models: nontransgenic (NTG), effective null for cMyBP-C (t/t), wild-type cMyBP-C expressed into t/t (WT(t/t)), and constitutively unphosphorylated cMyBP-C (AllP-(t/t)). We found that the absence of cMyBP-C in the t/t and the unphosphorylated cMyBP-C in the AllP-(t/t) resulted in a compressible cardiac myofilament lattice induced by rigor not observed in the NTG and WT(t/t). These results suggest that the presence and phosphorylation of the N-terminus of cMyBP-C provides structural support and radial rigidity to the myofilament lattice. Examination of myofilament longitudinal stiffness under rigor conditions demonstrated a significant reduction in cross-bridge-dependent stiffness in the t/t compared with NTG controls, but not in the AllP-(t/t) compared with WT(t/t) controls. The absence of cMyBP-C in the t/t and the unphosphorylated cMyBP-C in the AllP-(t/t) both resulted in a shorter myosin cross-bridge lifetime when myosin isoform was controlled. These data collectively suggest that cMyBP-C provides radial rigidity to the myofilament lattice through the N-terminus, and that disruption of the phosphorylation of cMyBP-C is sufficient to abolish this structural role of the N-terminus and shorten cross-bridge lifetime. Although the presence of cMyBP-C also provides longitudinal rigidity, phosphorylation of the N-terminus is not necessary to maintain longitudinal rigidity of the lattice, in contrast to radial rigidity.
authors.affiliation: Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, Vermont, USA. bmpalmer@uvm.edu
authors.forename: Bradley M
authors.initials: BM
authors.lastname: Palmer
authors.forename: Sakthivel
authors.initials: S
authors.lastname: Sadayappan
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Abbey E
authors.initials: AE
authors.lastname: Weith
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Previs
authors.forename: Tanya
authors.initials: T
authors.lastname: Bekyarova
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Irving
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Robbins
authors.forename: David W
authors.initials: DW
authors.lastname: Maughan
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D055595:Mechanical Phenomena; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism*; D010766:Phosphorylation; D013997:Time Factors; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D009218:Myosins; D000099163:Myosin Binding Protein C