Figure 7. Model for MuRF1/2 dependent type-II fiber trophicity and NFAT signaling control.

A) Drawing summarizing the main findings of the study. In WT mice type II fibers (pink) express MuRF1 (small green dots inside the fiber) in contrast to type I fibers (red) where MuRF1 is absent. After denervation (DEN), MuRF1 expression is further elevated in type II fibers, thereby decreasing their cross sectional area (WT DEN). In myofibrils from MuRF1-KO mice after DEN, type II fibers are preferentially spared from atrophy when compared to type I fiber tissues. In addition, MuRF1-deficient fibers lose their type II fiber identity as unloading evolves, migrating towards an intermediate state (represented by orange color).

B) Proposed model for MuRF1 signaling on type II muscle fibers. Modification of the myozenin-1 (MYOZ-1)/calcineurin and myozenin-2 (MYOZ-2)/calcineurin complex by MuRF1 and MuRF2 results in a downregulation of the calcineurin-NFAT pathway that opposes type-II hypertrophy. Therefore, combined deletion of MuRF1/MuRF2 might result in a diminished calcineurin-NFAT signaling, that interferes with the physiological maintenance of type II fibers.