| First Author | Lee CS | Year | 2014 |
| Journal | J Biol Chem | Volume | 289 |
| Issue | 37 | Pages | 25556-70 |
| PubMed ID | 25053409 | Mgi Jnum | J:338702 |
| Mgi Id | MGI:6780590 | Doi | 10.1074/jbc.M114.586289 |
| Citation | Lee CS, et al. (2014) Ligands for FKBP12 increase Ca2+ influx and protein synthesis to improve skeletal muscle function. J Biol Chem 289(37):25556-70 |
| abstractText | Rapamycin at high doses (2-10 mg/kg body weight) inhibits mammalian target of rapamycin complex 1 (mTORC1) and protein synthesis in mice. In contrast, low doses of rapamycin (10 mug/kg) increase mTORC1 activity and protein synthesis in skeletal muscle. Similar changes are found with SLF (synthetic ligand for FKBP12, which does not inhibit mTORC1) and in mice with a skeletal muscle-specific FKBP12 deficiency. These interventions also increase Ca(2+) influx to enhance refilling of sarcoplasmic reticulum Ca(2+) stores, slow muscle fatigue, and increase running endurance without negatively impacting cardiac function. FKBP12 deficiency or longer treatments with low dose rapamycin or SLF increase the percentage of type I fibers, further adding to fatigue resistance. We demonstrate that FKBP12 and its ligands impact multiple aspects of muscle function. |
