Special Issue: The Actin-Myosin Interaction in Muscle: Background and Overview

Abstract

Muscular contraction is a fundamental phenomenon in all animals; without it life as we know it would be impossible. The basic mechanism in muscle, including heart muscle, involves the interaction of the protein filaments myosin and actin. Motility in all cells is also partly based on similar interactions of actin filaments with non-muscle myosins. Early studies of muscle contraction have informed later studies of these cellular actin-myosin systems. In muscles, projections on the myosin filaments, the so-called myosin heads or cross-bridges, interact with the nearby actin filaments and, in a mechanism powered by ATP-hydrolysis, they move the actin filaments past them in a kind of cyclic rowing action to produce the macroscopic muscular movements of which we are all aware. In this special issue the papers and reviews address different aspects of the actin-myosin interaction in muscle as studied by a plethora of complementary techniques. The present overview provides a brief and elementary introduction to muscle structure and function and the techniques used to study it. It goes on to give more detailed descriptions of what is known about muscle components and the cross-bridge cycle using structural biology techniques, particularly protein crystallography, electron microscopy and X-ray diffraction. It then has a quick look at muscle mechanics and it summarises what can be learnt about how muscle works based on the other studies covered in the different papers in the special issue. A picture emerges of the main molecular steps involved in the force-producing process; steps that are also likely to be seen in non-muscle myosin interactions with cellular actin filaments. Finally, the remarkable advances made in studying the effects of mutations in the contractile assembly in causing specific muscle diseases, particularly those in heart muscle, are outlined and discussed.

Mass Spectrometric Profiling of Extraocular Muscle and Proteomic Adaptations in the mdx-4cv Model of Duchenne Muscular Dystrophy

“…Figure 2 b shows a Venn diagram of EOM versus diaphragm and illustrates the large cohort of overlapping expression of proteins belonging to the thick filament, the thin filament, the Z-disk, the M-band, auxiliary filaments and the sarcomere-associated cytoskeletal network [ 55 , 56 , 57 ]. Interestingly, elevated protein levels in EOMs included the myosin heavy chain isoforms myosin-2 (fast MyHC-IIa; MYH2) [ 51 ], myosin-13 (MyHC13; MYH13) [ 63 ], myosin-14 (MyHC14; MYH14) [ 58 , 59 ] and myosin-15 (MyHC15; MYH15) [ 58 , 59 ], as well as myosin light polypeptide 6 (MYL6; MLC-3 isoform) [ 60 ] and slow cardiac alpha-actin-1 (ACTC1) [ 64 ]. In contrast, diaphragm muscle contained apparently higher concentrations of myosin light chains MLC-2 (MYL2) and MLC-3 (MYL3), muscle alpha-actin-1 (ACTA1), the troponin isoforms TNNI1, TNNC1 and TNNT1 and myosin-binding protein MYBP-H [ 36 , 39 ].…”

LncRNAs in cardiac hypertrophy: From basic science to clinical application

“…Many sarcomeres contracting in series contract the myofibrils, causing shortening of the whole cardiac fibre (Figure 1). 19,20 Besides, the Ca 2+ is critical to generate contraction as myofilament activation and force development is largely dependent on intracellular Ca 2+ .The degree of myofilament Ca 2+ sensitivity is dynamically regulated by the Ca 2+ binding affinity of Tn complex. 21 TnT mutations account for approximately 15% of genotype-positive HCM cases.…”

“…Many sarcomeres contracting in series contract the myofibrils, causing shortening of the whole cardiac fibre (Figure 1). 19,20 …”

Inflammation-Induced Protein Unfolding in Airway Smooth Muscle Triggers a Homeostatic Response in Mitochondria

“…In ASM cells, agonist (e.g., acetylcholine—ACh)-induced increase in [Ca 2+ ] cyt leads to a contractile response through a signaling cascade that involves Ca 2+ binding to calmodulin (CaM), Ca 2+ /CaM mediated activation of myosin light chain kinase (MLCK), phosphorylation of the regulatory myosin light chain (rMLC 20 ), myosin heavy chain (MyHC) binding to actin (cross-bridge formation), attachment of actin filaments to the ASM membrane and force generation against an external load [ 2 , 14 , 15 ]. ASM force generation resulting from cross-bridge recruitment and cycling is driven by ATP hydrolysis [ 1 , 2 , 16 , 17 ] ( Figure 2 ). Recently, we showed that TNFα increases ASM force generation in response to muscarinic (ACh) stimulation [ 1 , 2 ].…”