From function to structure: how myofibrillogenesis influences the transverse-axial tubular system development and its peculiarities

Zuzana Sevcikova Tomaskova Katarina Mackova ^*

• Institute of Molecular Physiology and Genetics, Centre of Biosciences, Slovak Academy of Sciences, Bratislava, Slovakia

Transverse-axial tubular system (TATS) is the extension of sarcolemma growing to the cell interior providing sufficient calcium signaling to induce calcium release from sarcoplasmic reticulum cisternae and to stimulate the contraction of neighboring myofibrils. Interestingly, the development of TATS is delayed and matures during post-partum period. It starts with small invaginations near sarcolemma, proceeding with growing of irregular network, which is later assembled to the notably transversally oriented tubular network. Accumulating evidence supports the idea that the development of TATS is linked to cell dimensions, calcium signaling and increasing myofibrillar content orchestrated by electromechanical stimulation. However, the overall mechanism is not described yet. The topic of this review is the development of TATS with the emphasis on the irregular phase of the tubules growth. The traditional models of BIN1-related tubulation are also discussed. We summarized the recently described protein interactions during TATS development, mainly mediated by costameric and sarcomeric proteins, supporting the idea of the coupling sites between TATS and the myofibrils. We propose a hypothesis that the formation and final organization of the tubular system is driven by the simultaneously occurring development of the contractile apparatus under cycling electromechanical stimulus.