Figure 7. Schematic of sarcomeric α-actinin regulation of calcineurin signaling. α-Actinin-2 is differentially expressed in muscles without α-actinin-3.

Higher-affinity binding of calsarcin-2 for α-actinin-2 over α-actinin-3 and competitive binding of α-actinin-2 for calsarcin-2 lead to the increased release of calcineurin from calsarcin-2 inhibition in the absence of α-actinin-3. We propose that increased free (active) calcineurin activates downstream signaling and the slow myogenic program in α-actinin-3–deficient muscle.