The molecular basis of thin filament activation: from single molecule to muscle

Scientific Reports
Thomas LongyearEdward P Debold

Abstract

For muscles to effectively power locomotion, trillions of myosin molecules must rapidly attach and detach from the actin thin filament. This is accomplished by precise regulation of the availability of the myosin binding sites on actin (i.e. activation). Both calcium (Ca++) and myosin binding contribute to activation, but both mechanisms are simultaneously active during contraction, making their relative contributions difficult to determine. Further complicating the process, myosin binding accelerates the attachment rate of neighboring myosin molecules, adding a cooperative element to the activation process. To de-convolve these two effects, we directly determined the effect of Ca++ on the rate of attachment of a single myosin molecule to a single regulated actin thin filament, and separately determined the distance over which myosin binding increases the attachment rate of neighboring molecules. Ca++ alone increases myosin's attachment rate ~50-fold, while myosin binding accelerates attachment of neighboring molecules 400 nm along the actin thin filament.

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Citations

Jul 25, 2019·American Journal of Physiology. Cell Physiology·Matthew Unger, Edward P Debold
Aug 21, 2019·Proceedings of the National Academy of Sciences of the United States of America·Sarah R ClippingerMichael J Greenberg
Jun 27, 2018·International Journal of Molecular Sciences·Alf MånssonDilson E Rassier
Nov 2, 2018·Journal of Muscle Research and Cell Motility·Katelyn JarvisSam Walcott
Jul 12, 2020·Biophysical Journal·Mike WoodwardEdward P Debold

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Methods Mentioned

BETA
motility assay
motility measurements

Software Mentioned

MATLAB
ImageJ

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