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.