Molecular characterisation of transverse tubule development in skeletal muscle (2016-2019)

The transverse tubule system of skeletal muscle is an extensive plasma membrane domain that allows an action potential transmitted by the nerve to reach the depths of a muscle fibre and trigger calcium release in a synchronised fashion. The T-tubule system is a vital component of the skeletal muscle, frequently disrupted in muscle disease. This is exemplified by aberrant T-tubules and mutations in key T-tubule components in many human myopathies. However, the molecular mechanisms by which the T-tubule system, with its unique morphology and molecular composition, is generated are completely unknown. We will use advanced microscopic techniques together with systematic quantitative analyses to understand the process of T-tubule formation in real-time in a vertebrate model system. Proteomics will be used to identify key T-tubule components. This information will be used to identify early markers of T-tubule formation and then to test their involvement in T-tubule formation in the zebrafish model system and in mice.