NDLI: Using Fluorescent Myosin to Directly Visualize Cooperative Activation of Thin $Filaments^{*♦}$

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Using Fluorescent Myosin to Directly Visualize Cooperative Activation of Thin $Filaments^{*♦}$

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kad, Neil M. Desai, Rama Geeves, Michael A.
Description	Author Affiliation: Desai R ( From the School of Biosciences, University of Kent, Canterbury CT2 7NH, United Kingdom.); Geeves MA ( From the School of Biosciences, University of Kent, Canterbury CT2 7NH, United Kingdom.); Kad NM ( From the School of Biosciences, University of Kent, Canterbury CT2 7NH, United Kingdom n.kad@kent.ac.uk.)
Abstract	Contraction of striated muscle is tightly regulated by the release and sequestration of calcium within myocytes. At the molecular level, calcium modulates myosin's access to the thin filament. Once bound, myosin is hypothesized to potentiate the binding of further myosins. Here, we directly image single molecules of myosin binding to and activating thin filaments. Using this approach, the cooperative binding of myosin along thin filaments has been quantified. We have found that two myosin heads are required to laterally activate a regulatory unit of thin filament. The regulatory unit is found to be capable of accommodating 11 additional myosins. Three thin filament activation states possessing differential myosin binding capacities are also visible. To describe this system, we have formulated a simple chemical kinetic model of cooperative activation that holds across a wide range of solution conditions. The stochastic nature of activation is strongly highlighted by data obtained in sub-optimal activation conditions where the generation of activation waves and their catastrophic collapse can be observed. This suggests that the thin filament has the potential to be turned fully on or off in a binary fashion.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	4
Volume Number	290
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2015-01-23
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Actin Cytoskeleton Chemistry Fluorescent Dyes Myosins Actins Adenosine Triphosphate Calcium Hydrolysis Muscle Contraction Physiology Muscle, Skeletal Metabolism Myosin Type II Normal Distribution Protein Binding Sarcomeres Stochastic Processes Tropomyosin Troponin Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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