title: Interplay between the overlapping ends of tropomyosin and the N terminus of cardiac troponin T affects tropomyosin states on actin.
abstract: The functional significance of the molecular swivel at the head-to-tail overlapping ends of contiguous tropomyosin (Tm) dimers in striated muscle is unknown. Contractile measurements were made in muscle fibers from transgenic (TG) mouse hearts that expressed a mutant α-Tm (Tm(H276N)). We also reconstituted mouse cardiac troponin T (McTnT) N-terminal deletion mutants, McTnT(1-44Δ) and McTnT(45-74Δ), into muscle fibers from Tm(H276N). For controls, we used the wild-type (WT) McTnT because altered effects could be correlated with the mutant forms of McTnT. Tm(H276N) slowed crossbridge (XB) detachment rate (g) by 19%. McTnT(1-44Δ) attenuated Ca(2+)-activated maximal tension against Tm(WT) (36%) and Tm(H276N) (38%), but sped g only against Tm(H276N) by 35%. The rate of tension redevelopment decreased (17%) only in McTnT(1-44Δ) + Tm(H276N) fibers. McTnT(45-74Δ) attenuated tension (19%) and myofilament Ca(2+) sensitivity (pCa50=5.93 vs. 6.00 in the control fibers) against Tm(H276N), but not against Tm(WT) background. Thus, altered XB cycling kinetics decreased the fraction of strongly bound XBs in McTnT(1-44Δ) + Tm(H276N) fibers, whereas diminished thin-filament cooperativity attenuated tension in McTnT(45-74Δ) + Tm(H276N) fibers. In summary, our study is the first to show that the interplay between the N terminus of cTnT and the overlapping ends of contiguous Tm effectuates different states of Tm on the actin filament.
authors.affiliation: Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-6520, USA.
authors.forename: Ranganath
authors.initials: R
authors.lastname: Mamidi
authors.forename: John Jeshurun
authors.initials: JJ
authors.lastname: Michael
authors.forename: Mariappan
authors.initials: M
authors.lastname: Muthuchamy
authors.forename: Murali
authors.initials: M
authors.lastname: Chandra
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D051379:Mice; D008822:Mice, Transgenic; D054792:Muscle, Striated / Q000378:metabolism; D009200:Myocardial Contraction / Q000235:genetics / Q000502:physiology; D014335:Tropomyosin / Q000235:genetics / Q000378:metabolism*; D020107:Troponin T / Q000378:metabolism*
chemical_list: D000199:Actins; D014335:Tropomyosin; D020107:Troponin T; D002118:Calcium
keywords: calcium-activated tension; molecular swivel; myofilament Ca2+ sensitivity; myofilament cooperativity; thin-filament activation