scholarly journals 1P144 The Troponin Globular Portion Binding Domain of Tropomyosin is Critical for Ca^-Dependent Regularion of Striated Muscle Thin Filament

2004 ◽  
Vol 44 (supplement) ◽  
pp. S65
Author(s):  
A. Sakuma ◽  
Y. Shitaka ◽  
C. kimura ◽  
K. Sakiyama ◽  
M. Miki
Keyword(s):  
Thin Filament ◽  
Striated Muscle ◽  
Binding Domain ◽  
Muscle Thin Filament

scholarly journals Role of Actin C-Terminus in Regulation of Striated Muscle Thin Filament

2008 ◽  
Vol 94 (4) ◽  
pp. 1341-1347 ◽  
Author(s):  
Masłgorzata Śliwińska ◽  
Radosław Skórzewski ◽  
Joanna Moraczewska
Keyword(s):  
Thin Filament ◽  
Striated Muscle ◽  
C Terminus ◽  
Muscle Thin Filament

scholarly journals Knockout of Lmod2 results in shorter thin filaments followed by dilated cardiomyopathy and juvenile lethality

2015 ◽  
Vol 112 (44) ◽  
pp. 13573-13578 ◽  
Author(s):  
Christopher T. Pappas ◽  
Rachel M. Mayfield ◽  
Christine Henderson ◽  
Nima Jamilpour ◽  
Cathleen Cover ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Thin Filament ◽  
Striated Muscle ◽  
Heart Function ◽  
Contractile Force ◽  
Actin Binding ◽  
Actin Assembly ◽  
Thin Filaments ◽  
Filament Assembly ◽  
Muscle Thin Filament

Leiomodin 2 (Lmod2) is an actin-binding protein that has been implicated in the regulation of striated muscle thin filament assembly; its physiological function has yet to be studied. We found that knockout of Lmod2 in mice results in abnormally short thin filaments in the heart. We also discovered that Lmod2 functions to elongate thin filaments by promoting actin assembly and dynamics at thin filament pointed ends. Lmod2-KO mice die as juveniles with hearts displaying contractile dysfunction and ventricular chamber enlargement consistent with dilated cardiomyopathy. Lmod2-null cardiomyocytes produce less contractile force than wild type when plated on micropillar arrays. Introduction of GFP-Lmod2 via adeno-associated viral transduction elongates thin filaments and rescues structural and functional defects observed in Lmod2-KO mice, extending their lifespan to adulthood. Thus, to our knowledge, Lmod2 is the first identified mammalian protein that functions to elongate actin filaments in the heart; it is essential for cardiac thin filaments to reach a mature length and is required for efficient contractile force and proper heart function during development.

scholarly journals Force Spectroscopy Reveals Multiple “Closed States” of the Muscle Thin Filament

2011 ◽  
Vol 286 (27) ◽  
pp. 24135-24141 ◽  
Author(s):  
Vijay S. Rao ◽  
Amy M. Clobes ◽  
William H. Guilford
Keyword(s):  
Actin Filaments ◽  
Thin Filament ◽  
Striated Muscle ◽  
Critical Role ◽  
Laser Trap ◽  
Myosin S1 ◽  
State Affect ◽  
Myosin Binding ◽  
Three State Model ◽  
Muscle Thin Filament

Tropomyosin (Tm) plays a critical role in regulating the contraction of striated muscle. The three-state model of activation posits that Tm exists in three positions on the thin filament: “blocked” in the absence of calcium when myosin cannot bind, “closed” when calcium binds troponin and Tm partially covers the myosin binding site, and “open” after myosin binding forces Tm completely off neighboring sites. However, we recently showed that actin filaments decorated with phosphorylated Tm are driven by myosin with greater force than bare actin filaments. This result cannot be explained by simple steric hindrance and suggests that Tm may have additional effects on actin-myosin interactions. We therefore tested the hypothesis that Tm and its phosphorylation state affect the rate at which single actin-myosin bonds form and rupture. Using a laser trap, we measured the time necessary for the first bond to form between actin and rigor heavy meromyosin and the load-dependent durations of those bonds. Measurements were repeated in the presence of subsaturating myosin-S1 to force Tm from the closed to the open state. Maximum bond lifetimes increased in the open state, but only when Tm was phosphorylated. While the frequency with which bonds formed was extremely low in the closed state, when a bond did form it took significantly less time to do so than with bare actin. These data suggest there are at least two closed states of the thin filament, and that Tm provides additional points of contact for myosin.

scholarly journals Mechanical contribution to muscle thin filament activation

2020 ◽  
Vol 295 (47) ◽  
pp. 15913-15922
Author(s):  
Henry G. Zot ◽  
P. Bryant Chase ◽  
Javier E. Hasbun ◽  
Jose R. Pinto
Keyword(s):  
Relative Density ◽  
Thin Filament ◽  
Chemical Potential ◽  
Striated Muscle ◽  
Waiting Times ◽  
Regulatory Proteins ◽  
Thin Filaments ◽  
Short Run ◽  
Muscle Thin Filament ◽  
Thermodynamic Mechanism

Vertebrate striated muscle thin filaments are thought to be thermodynamically activated in response to an increase in Ca2+ concentration. We tested this hypothesis by measuring time intervals for gliding runs and pauses of individual skeletal muscle thin filaments in cycling myosin motility assays. A classic thermodynamic mechanism predicts that if chemical potential is constant, transitions between runs and pauses of gliding thin filaments will occur at constant rate as given by a Poisson distribution. In this scenario, rate is given by the odds of a pause, and hence, run times between pauses fit an exponential distribution that slopes negatively for all observable run times. However, we determined that relative density of observed run times fits an exponential only at low Ca2+ levels that activate filament gliding. Further titration with Ca2+, or adding excess regulatory proteins tropomyosin and troponin, shifted the relative density of short run times to fit the positive slope of a gamma distribution, which derives from waiting times between Poisson events. Events that arise during a run and prevent the chance of ending a run for a random interval of time account for the observed run time distributions, suggesting that the events originate with cycling myosin. We propose that regulatory proteins of the thin filament require the mechanical force of cycling myosin to achieve the transition state for activation. During activation, combinations of cycling myosin that contribute insufficient activation energy delay deactivation.

Characterization of Three Regulatory States of the Striated Muscle Thin Filament

2002 ◽  
Vol 323 (3) ◽  
pp. 475-489 ◽  
Author(s):  
Juliette Van Dijk ◽  
Alex E Knight ◽  
Justin E Molloy ◽  
Patrick Chaussepied
Keyword(s):  
Thin Filament ◽  
Striated Muscle ◽  
Muscle Thin Filament

Orientation of actin filaments during motion in motility assay

1995 ◽  
Vol 53 ◽  
pp. 52-53
Author(s):  
J. Borejdo ◽  
S. Burlacu
Keyword(s):  
Actin Filaments ◽  
Thin Filament ◽  
Striated Muscle ◽  
Myosin Head ◽  
Classical Method ◽  
Polarization Of Fluorescence ◽  
Single Protein ◽  
Intracellular Organelles ◽  
Change Orientation ◽  
Active Entity

Polarization of fluorescence is a classical method to assess orientation or mobility of macromolecules. It has been a common practice to measure polarization of fluorescence through a microscope to characterize orientation or mobility of intracellular organelles, for example anisotropic bands in striated muscle. Recently, we have extended this technique to characterize single protein molecules. The scientific question concerned the current problem in muscle motility: whether myosin heads or actin filaments change orientation during contraction. The classical view is that the force-generating step in muscle is caused by change in orientation of myosin head (subfragment-1 or SI) relative to the axis of thin filament. The molecular impeller which causes this change resides at the interface between actin and SI, but it is not clear whether only the myosin head or both SI and actin change orientation during contraction. Most studies assume that observed orientational change in myosin head is a reflection of the fact that myosin is an active entity and actin serves merely as a passive "rail" on which myosin moves.

scholarly journals Tropomodulin isoforms regulate thin filament pointed-end capping and skeletal muscle physiology

2010 ◽  
Vol 189 (1) ◽  
pp. 95-109 ◽  
Author(s):  
David S. Gokhin ◽  
Raymond A. Lewis ◽  
Caroline R. McKeown ◽  
Roberta B. Nowak ◽  
Nancy E. Kim ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Thin Filament ◽  
Striated Muscle ◽  
Fiber Type ◽  
Actin Dynamics ◽  
Muscle Physiology ◽  
Skeletal Muscle Function ◽  
Capping Proteins ◽  
Locomotor Deficits ◽  
End Capping

During myofibril assembly, thin filament lengths are precisely specified to optimize skeletal muscle function. Tropomodulins (Tmods) are capping proteins that specify thin filament lengths by controlling actin dynamics at pointed ends. In this study, we use a genetic targeting approach to explore the effects of deleting Tmod1 from skeletal muscle. Myofibril assembly, skeletal muscle structure, and thin filament lengths are normal in the absence of Tmod1. Tmod4 localizes to thin filament pointed ends in Tmod1-null embryonic muscle, whereas both Tmod3 and -4 localize to pointed ends in Tmod1-null adult muscle. Substitution by Tmod3 and -4 occurs despite their weaker interactions with striated muscle tropomyosins. However, the absence of Tmod1 results in depressed isometric stress production during muscle contraction, systemic locomotor deficits, and a shift to a faster fiber type distribution. Thus, Tmod3 and -4 compensate for the absence of Tmod1 structurally but not functionally. We conclude that Tmod1 is a novel regulator of skeletal muscle physiology.

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