Distinct troponin C isoform requirements in cardiac and skeletal muscle.
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ABSTRACT:
SUBMITTER: Sogah VM
PROVIDER: S-EPMC2965274 | biostudies-literature | 2010 Nov
REPOSITORIES: biostudies-literature
Publications
Distinct troponin C isoform requirements in cardiac and skeletal muscle.
Sogah Vanessa M VM Serluca Fabrizio C FC Fishman Mark C MC Yelon Deborah L DL Macrae Calum A CA Mably John D JD
Developmental dynamics : an official publication of the American Association of Anatomists 20101101 11
The zebrafish mutant silent partner is characterized by a dysmorphic, non-contractile ventricle resulting in an inability to generate normal blood flow. We have identified the genetic lesion in the zebrafish homolog of the slow twitch skeletal/cardiac troponin C gene. Although human troponin C1 (TNNC1) is expressed in both cardiac and skeletal muscle, duplication of this gene in zebrafish has resulted in tissue-specific partitioning of troponin C expression and function. Mutation of the zebrafis ...[more]
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Project description:Time-resolved changes in the conformation of troponin in the thin filaments of skeletal muscle were followed during activation in situ by photolysis of caged calcium using bifunctional fluorescent probes in the regulatory and the coiled-coil (IT arm) domains of troponin. Three sequential steps in the activation mechanism were identified. The fastest step (1,100 s(-1)) matches the rate of Ca(2+) binding to the regulatory domain but also dominates the motion of the IT arm. The second step (120 s(-1)) coincides with the azimuthal motion of tropomyosin around the thin filament. The third step (15 s(-1)) was shown by three independent approaches to track myosin head binding to the thin filament, but is absent in the regulatory head. The results lead to a four-state structural kinetic model that describes the molecular mechanism of muscle activation in the thin filament-myosin head complex under physiological conditions.
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| S-EPMC231397 | biostudies-other