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Cover Image
Cover Image
ON THE COVER
The actin-capping protein CapZ integrates mechanosignaling pathways, such as phosphorylation and phosphatidylinositol 4,5-bisphosphate (PIP2) binding, to regulate muscle growth in response to mechanical loading by substrates of varying stiffness. Here, PIP2 is localized to the Z-disks of a neonatal rat ventricular myocyte grown on a stiff glass substrate, fixed and stained for α-actinin (red) and PIP2 (green). Results show the C-terminal domain of the CapZβ1 subunit stabilizes CapZ and PIP2 interactions, which may have relevance to fibrotic heart disease. See page 660. - PDF Icon PDF LinkTable of Contents
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Editorials
Progress on the regulation of myofibrillar function: Part 2
The second of two special issues on contractile systems charts further progress towards an understanding of myofilament regulation.
Commentary
Getting into the thick (and thin) of it
Irving and Craig reflect on new work showing that thick filament activation involves myosin motors returning to their OFF state during diastole.
What a drag!: Skeletal myosin binding protein-C affects sarcomeric shortening
Colson discusses a recent investigation of the functional effect of slow myosin binding protein-C in slow-twitch skeletal muscle fibers.
Elastic domains of giant proteins in striated muscle: Modeling compliance with rulers
Chase examines a study using the MUSICO model of striated muscle to evaluate the function of giant elastic proteins titin and nebulin.
Milestones in Physiology
The enduring relationship between myosin enzymatic activity and the speed of muscle contraction
Moss and Solaro recall Bárány’s landmark study that identified myosin ATPase as the fundamental driver of contraction speed.
Viewpoint
Investigation into the mechanism of thin filament regulation by transient kinetics and equilibrium binding: Is there a conflict?
The authors examine the apparent discrepancies from studies aimed at understanding the mechanism of thin filament regulation.
Research Articles
Developmental increase in β-MHC enhances sarcomere length–dependent activation in the myocardium
The expression of β-myosin heavy chain (β-MHC) in the guinea pig heart increases during postnatal development. Reda et al. show that this increase in β-MHC enhances length-mediated increases in myofilament Ca2+ sensitivity and sarcomere length–dependent changes in contractile function.
Regulation of myofilament force and loaded shortening by skeletal myosin binding protein C
Myosin binding protein C (MyBP-C) is thought to regulate the contraction of skeletal muscle. Robinett et al. show that phosphorylation of slow skeletal MyBP-C modulates contraction by recruiting cross-bridges, modifying cross-bridge kinetics, and altering internal drag forces in the C-zone.
CapZ integrates several signaling pathways in response to mechanical stiffness
Changes in mechanical load, hormones, or metabolic stress provoke remodeling of the actin-based thin filaments within muscle fibers. Solís and Russell show that several signaling pathways converge at the actin-capping protein CapZ to regulate muscle fiber growth in response to mechanical stiffness and neurohumoral signaling.
Deletion of Enigma Homologue from the Z-disc slows tension development kinetics in mouse myocardium
Enigma Homologue (ENH) is a Z-disc protein whose loss causes cardiomyopathy, but whose function in muscle mechanics is poorly understood. Gregorich et al. show that ENH affects tension redevelopment in mouse myocardium, possibly by altering cross-bridge cycling kinetics or the compliance of the Z-disc.
Nebulin and titin modulate cross-bridge cycling and length-dependent calcium sensitivity
The contractility of striated muscle can be modulated by various mutations in nebulin and titin present in human disease. Mijailovich et al. perform computational simulations coupled with experimental observations to provide insights into the mechanisms by which mutations in these proteins cause disease phenotypes.
