Formation, Contraction, and Mechanotransduction of Myofribrils in Cardiac Development: Clues from Genetics

Figure 1

Schematic representation of the structures of the myofibrils responsible of contraction, sensation, and transduction of mechanical stimuli in the developing heart. Force is generated by the thick filaments formed by myosin heavy chain (amhc, MYH6, MYH7) associated with myosin regulatory (Myl7) and essential light chains and their interaction with the thin filaments, formed by actin (ACTC1, cfk) and troponin T (Tnnt2), TCAP and TMOD, amongst others. Titin spans a half of the sarcomere, from the Z-Disc (where it interacts with TCAP and MLP) to the M-band. One of its intermediate segments, the N2A-region, acts as a mechanotransducer and binds CARP, DARP, and ANKR2. The peripheral myofibrils of the cardiomyocytes are linked to integrins embedded in the cell membrane (sarcolemma) by means of the focal adhesion complexes of the costameres, formed by FAK ERK1 and ERK2, amongst others. In response to mechanical stimulation, proteins bound to titin (CARP, DARP, and ANKR2), proteins of the Z-Disc (MLP, PKCε), as well as FAK, ERK1, and ERK2, located to the focal adhesion complexes, translocate to the nucleus, where they interact with cardiac transcription factors to modify gene expression.