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Skeletal Muscle Disease Due to Mutations in Tropomyosin, Troponin and Cofilin

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The Sarcomere and Skeletal Muscle Disease

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 642))

Abstract

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 expression pattern that enables cardiac, slow skeletal (type 1) and fast skeletal (type 2) muscle fibers to have distinct contractile properties. Mutations in all components of this complex have been associated with skeletal muscle disease. The first disease associations were with nemaline myopathy, but recently other congenital myopathies (‘cap disease,’ congenital fiber type disproportion) and other clinical entities (distal arthrogryposis, multiple pterygium syndrome) have been linked to mutations. A homozygous mutation in CFL2, the gene for muscle cofilin, has been associated with nemaline myopathy in one family to date. Researchers have begun to decipher the mechanisms by which these mutations result in muscle weakness and contractures using a variety of in vitro assays to assess the effects of individual mutations on protein function and on sarcomere dynamics.

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  1. Institute for Neuromuscular Research, Children’s Hospital at Westmead, Discipline of Pediatrics and Child Health, University of Sydney, Sydney, Australia

    Nigel F. Clarke

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  1. Nigel F. Clarke
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  1. Centre for Medical Research, University of Western Australia, Western Australian Institute for Medical Research, Nedlands, Western Australia, Australia

    Nigel G. Laing PhD

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© 2008 Landes Bioscience and Springer Science+Business Media

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Clarke, N.F. (2008). Skeletal Muscle Disease Due to Mutations in Tropomyosin, Troponin and Cofilin. In: Laing, N.G. (eds) The Sarcomere and Skeletal Muscle Disease. Advances in Experimental Medicine and Biology, vol 642. Springer, New York, NY. https://doi.org/10.1007/978-0-387-84847-1_4

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