Amysterious version of the protein calcineurin turns out to be a healer that helps refurbish damaged muscle, as Lara-Pezzi et al. report. The molecule promotes cell division and drives away immune cells that can obstruct repair.
Sparked by rising calcium levels, calcineurin flips on transcription factors that control everything from immune responses to heart development to muscle cell differentiation. The two halves of the protein, CnA and CnB, come in several forms. Scientists discovered a new version of CnA, known as CnAβ1, nearly 20 years ago, but they knew little about its function.
Now, the researchers show that, with CnAβ1, undifferentiated muscle cells divide more quickly and are less likely to specialize. Calcineurin usually exerts its influence by activating the NFAT transcription factors. CnAβ1, however, activated a different signaling pathway and blocked the transcription factor FoxO.
CnAβ1 also sped regrowth of damaged muscle, the team shows. In mice that had received an injection of a muscle-destroying poison, boosting CnAβ1 levels caused an increase in the number of active muscle stem cells and a thickening of regenerating muscle fibers. CnAβ1 also trimmed the number of macrophages at the injury site and limited accumulation of fresh extracellular matrix.
Thus CnAβ1 helps muscle heal by encouraging cell division, calming inflammation, and limiting scarring, leaving more room for new muscle cells. The next question, the scientists say, is whether the variant is important for other fast-dividing cells, such as stem cells and tumor cells.