Interplay between the overlapping ends of tropomyosin and the N terminus of cardiac troponin T affects tropomyosin states on actin

Ranganath Mamidi; John Jeshurun Michael; Mariappan Muthuchamy; Murali Chandra

doi:10.1096/fj.13-232363

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Interplay between the overlapping ends of tropomyosin and the N terminus of cardiac troponin T affects tropomyosin states on actin

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Interplay between the overlapping ends of tropomyosin and the N terminus of cardiac troponin T affects tropomyosin states on actin

Ranganath Mamidi, John Jeshurun Michael, Mariappan Muthuchamy and Murali Chandra

The FASEB journal, Vol.27(9), pp.3848-3859

09/2013

DOI: https://doi.org/10.1096/fj.13-232363

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https://hdl.handle.net/2376/102553

PMCID: PMC3752546

PMID: 23748972

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Abstract

Research Communications

myofilament cooperativity

myofilament Ca2+ sensitivity

molecular swivel

calcium-activated tension

thin-filament activation

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 1–44 Δ and McTnT 45–74 Δ , 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 1–44 Δ 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 1–44 Δ + Tm H276N fibers. McTnT 45–74 Δ attenuated tension (19%) and myofilament Ca 2+ sensitivity (pCa 50 =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 1–44 Δ + Tm H276N fibers, whereas diminished thin-filament cooperativity attenuated tension in McTnT 45–74 Δ + 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. —Mamidi, R., Michael, J. J., Muthuchamy, M., Chandra, M. Interplay between the overlapping ends of tropomyosin and the N terminus of cardiac troponin T affects tropomyosin states on actin.

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Title: Interplay between the overlapping ends of tropomyosin and the N terminus of cardiac troponin T affects tropomyosin states on actin
Creators: Ranganath Mamidi - Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA; and
John Jeshurun Michael - Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA; and
Mariappan Muthuchamy - Department of Systems Biology and Translational Medicine, Cardiovascular Research Institute, Division of Lymphatic Biology, Texas A&M Health Science Center College of Medicine, College Station, Texas, USA
Murali Chandra - Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA; and
Publication Details: The FASEB journal, Vol.27(9), pp.3848-3859
Academic Unit: Integrative Physiology and Neuroscience, Department of
Publisher: Federation of American Societies for Experimental Biology; Bethesda, MD, USA
Identifiers: 99900546654201842
Language: English
Resource Type: Journal article