Figure 2. Molecular Signaling Pathways Link Changes in Contractile Activity to Changes in Gene Expression That Establish Myofiber Diversity.

A tonic pattern of motor nerve activity promotes changes in intracellular calcium that trigger a variety of intracellular events that modify the function of nuclear transcription factors. The pathway transduced by calcineurin and NFAT is highlighted in larger type. Other signals are received by cell surface receptors to activate similar or parallel signaling events. Signaling proteins that participate in transducing effects of contractile activity to specific genes include ion channels (TRP), scaffolding proteins (Homer), protein phosphatases and protein kinases (calcineurin, CAMK, p38MAPK), DNA-binding transcription factors (shown in red; NFAT, MEF2, PGC-1, ATF2), and endogenous inhibitors (shown in blue; GSK3, HDAC, and MCIP) (inhibitors antagonize gene activation via the pathways indicated, in some cases acting as negative feedback regulators).