Chapter

The Sarcomere and Skeletal Muscle Disease

Volume 642 of the series Advances in Experimental Medicine and Biology pp 99-115

Third Filament Diseases

  • Bjarne UddAffiliated withDepartment of Neurology, Tampere University Hospital and Medical SchoolFolkhälsan Institute of Genetics, Biomedicum, C304, University of HelsinkiDepartment of Neurology, Vasa Central Hospital

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Abstract

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 filament system provides support to the contractile filament systems during development and mature states including mechanical properties and regulatory signaling functions. The first mutations in the third filament system causing human muscle disease were identified in calpain 3 in 1995, followed by telethonin and titin. In spite of some early ideas on what is going wrong in the muscle cells based on the defective proteins, the exact molecular pathomechanisms leading to muscle atrophy in patients with these disorders are still unknown. However, preparations for direct trials of gene therapy have already been launched, at least for calpainopathy.