The backbone of the third filament system of the sarcomere is the huge titin molecule, spanning from the sarcomeric Z‑disc to the M‑line. Proteins in direct interaction and functionally integrated with titin, such as calpain 3 and telethonin, are part of the third filament system. The third...

Myocytes are characterized by the presence of highly specialized cytoskeletal structures that are part of regularly spaced functional units distributed over long distances. In this chapter we discuss previously published evidence as well as novel data showing that the proper positioning and...

Mutations in actin and tropomyosin, identified in patients with myopathic disease have been used in tissue culture models and functional studies with a view to understand how these mutations impact on skeletal muscle structure and function and result in muscle weakness. The likely mode of...

Desminopathy is one of the most common intermediate filament human disorders associated with mutations in closely interacting proteins, desmin and alphaB‑crystallin. The inheritance pattern in familial desminopathy is characterized as autosomal dominant or autosomal recessive, but many cases...

Hereditary myosin myopathies are a newly emerged group of diseases caused by mutations in skeletal muscle myosin heavy chain (MyHC) genes. The phenotypes of these diseases are varied, ranging from prenatal nonprogressive arthrogrypotic syndromes to adult‑onset progressive muscle weakness. They...

Skeletal muscle α‑actin is the principal protein component of the adult skeletal muscle thin filament. The interaction between skeletal muscle α‑actin and the various myosin heavy chain proteins in the different muscle fibre types generates the force of muscle contraction. Skeletal muscle...

Nebulin is an enormous protein of the muscle sarcomere. It is a determinant of thin filament length, Z‑disk structure and fiber contractility. The nebulin gene contains four regions of alternative splicing, providing a wealth of different isoforms of the protein. The precise function of these...

Tropomyosin (Tm) and the troponins (troponin I, troponin T and troponin C) are proteins that work cooperatively to regulate muscle contraction, making actin‑myosin interactions sensitive to cytosolic calcium levels. Several isoforms exist for each component in this group, each having a specific...

Recent studies have identified disease‑causing mutations in four genes that encode Z‑disk proteins. Mutations in myotilin (MYOT), ZASP and filamin C (FLNC) encoding genes cause autosomal dominant myopathy that manifests in adulthood. The clinical features and morphological changes in...

Thin filament integrity is important for the ordered structure and function of skeletal muscles. Mutations within genes that encode thin filament and thin filament‑associated proteins can cause muscle disruption, fiber atrophy and alter fiber type composition, leading to muscle weakness....

Model organisms are vital to our understanding of human muscle biology and disease. The potential of the nematode Caenorhabditis elegans, the fruitfly, Drosophila melanogaster and the zebrafish, Danio rerio, as model genetic organisms for the study of human muscle disease is discussed by...

Striated muscle owes its name to the microscopic appearance, caused by the longitudinal alignment of thousands of highly ordered contractile units, the sarcomeres. The assembly (and disassembly) of these multiprotein complexes (sarcomere assembly or sarcomerogenesis) follows ordered pathways,...

Skeletal muscle has a remarkable ability to rapidly adjust to changes in physiological requirements. This includes hypertrophic muscle growth and the atrophic loss of muscle mass, both of which occur in response to hormonal, endocrine and mechanical stimuli. In ageing muscle, sarcopenia (the loss...

Acquired neuromuscular disorders have been shown to be very common in critically ill patients receiving prolonged mechanical ventilation in the intensive care unit (ICU). Acute Quadriplegic Myopathy (AQM) is a specific acquired myopathy in ICU patients. Patients with AQM are characterized by...

No curative treatment currently exists for patients with skeletal myopathies caused by defects in sarcomeric proteins though symptomatic treatments including orthoses, night‑time ventilation, or mechanical ventilation can provide major benefits. The molecular genetic discovery era has enabled...