| First Author | Kramerova I | Year | 2018 |
| Journal | Hum Mol Genet | Volume | 27 |
| Issue | 9 | Pages | 1642-1653 |
| PubMed ID | 29528394 | Mgi Jnum | J:261418 |
| Mgi Id | MGI:6155411 | Doi | 10.1093/hmg/ddy071 |
| Citation | Kramerova I, et al. (2018) Calpain 3 and CaMKIIbeta signaling are required to induce HSP70 necessary for adaptive muscle growth after atrophy. Hum Mol Genet 27(9):1642-1653 |
| abstractText | Mutations in CAPN3 cause autosomal recessive limb girdle muscular dystrophy 2A. Calpain 3 (CAPN3) is a calcium dependent protease residing in the myofibrillar, cytosolic and triad fractions of skeletal muscle. At the triad, it colocalizes with calcium calmodulin kinase IIbeta (CaMKIIbeta). CAPN3 knock out mice (C3KO) show reduced triad integrity and blunted CaMKIIbeta signaling, which correlates with impaired transcriptional activation of myofibrillar and oxidative metabolism genes in response to running exercise. These data suggest a role for CAPN3 and CaMKIIbeta in gene regulation that takes place during adaptation to endurance exercise. To assess whether CAPN3- CaMKIIbeta signaling influences skeletal muscle remodeling in other contexts, we subjected C3KO and wild type mice to hindlimb unloading and reloading and assessed CaMKIIbeta signaling and gene expression by RNA-sequencing. After induced atrophy followed by 4 days of reloading, both CaMKIIbeta activation and expression of inflammatory and cellular stress genes were increased. C3KO muscles failed to activate CaMKIIbeta signaling, did not activate the same pattern of gene expression and demonstrated impaired growth at 4 days of reloading. Moreover, C3KO muscles failed to activate inducible HSP70, which was previously shown to be indispensible for the inflammatory response needed to promote muscle recovery. Likewise, C3KO showed diminished immune cell infiltration and decreased expression of pro-myogenic genes. These data support a role for CaMKIIbeta signaling in induction of HSP70 and promotion of the inflammatory response during muscle growth and remodeling that occurs after atrophy, suggesting that CaMKIIbeta regulates remodeling in multiple contexts: endurance exercise and growth after atrophy. |
