Ankrd2 in Mechanotransduction and Oxidative Stress Response in Skeletal Muscle: New Cues for the Pathogenesis of Muscular Laminopathies

Figure 3

Proposed pathogenic mechanisms in which Ankrd2 might be involved. In healthy muscle cells, physiological amounts of ROS or muscle differentiation induce Ankrd2 phosphorylation by Akt2 [15] and translocation into the nucleus, by binding to A-type lamins (black mesh) [98]. In the nucleus, Ankrd2 modulates the activation of muscle-specific and stress-responsive genes, by interacting with transcription factors (see text and Table 1 for references). In laminopathic muscle cells, mutated A-type lamins (red mesh) even in the absence of external stimuli recruit Ankrd2 into the nucleus. In addition to the already reported consequences, including an anomalous increase of ROS release, myogenic delay, and apoptotic cell death [98], potential pathogenic mechanisms, through which the altered nuclear localization of Ankrd2 might contribute to the pathogenesis of LMNA-related muscular disorders, are proposed.