Dysferlin: going molecular
Wow, this has been a true publication odyssey: Julia's PhD project is finally accepted! Congrats to Julia and many collaborators for great work and a great publication!
The T-tubule system of the skeletal muscle is an extensive membrane system that invaginates from the plasma membrane and forms a highly organized network throughout the whole muscle. This membrane system is essentially needed for muscle contraction, as it leads the action potential from the plasma membrane into the muscle fibre thereby initiating contraction. So far, the mechanism for biogenesis, function and maintenance of this cellular organelle are only partially understood and only fewproteins involved in these processes are known so far. One candidate that had already been localized to the T-tubule system and that had been indirectly associated with a function in T-tubule biogenesis is Dysferlin. This huge protein (230 kDa!) contains a transmembrane domain and several C2 domains. C2 domains are often involved in membrane interaction and fusion processes. Therefore, we aimed to analyse the cellular and molecular function of Dysferlin in more detail. In in vitro and in vivo experiments, we found that Dysferlin actually is able to mediate formation of T-tubule-like membranes. We also show that dysferlin is crucially needed for maintenance of proper calcium homeostasis in the skeletal muscle. https://pubmed.ncbi.nlm.nih.gov/28104817/