Fig. 6

Molecular mechanisms associated with TPM3-related myopathy. Studies performed in reconstituted thin filaments in vitro and in patient muscle fibers showed that even minor changes within the tropomyosin structure can have major impacts on its function. Mutations in the TPM3 gene (amino acid position are indicated in blue) can affect interaction between tropomyosin (Tpm) and actin, troponin, tropomodulin (Tmod) as well as other tropomyosin isoforms. These alterations can lead to thin filament dysfunction and impaired acto-myosin interaction during muscle contraction. Additionally, secondary disease mechanisms involving mitochondria, muscle development, ion channels and fatty acid metabolism are also depicted. Several therapeutic strategies have been developed to alleviate muscle weakness (shown in red). However, most of these strategies have not yet been tested in patients