| First Author | Whitlock JM | Year | 2018 |
| Journal | J Gen Physiol | Volume | 150 |
| Issue | 11 | Pages | 1498-1509 |
| PubMed ID | 30257928 | Mgi Jnum | J:325166 |
| Mgi Id | MGI:6871563 | Doi | 10.1085/jgp.201812097 |
| Citation | Whitlock JM, et al. (2018) Anoctamin 5/TMEM16E facilitates muscle precursor cell fusion. J Gen Physiol 150(11):1498-1509 |
| abstractText | Limb-girdle muscular dystrophy type 2L (LGMD2L) is a myopathy arising from mutations in ANO5; however, information about the contribution of ANO5 to muscle physiology is lacking. To explain the role of ANO5 in LGMD2L, we previously hypothesized that ANO5-mediated phospholipid scrambling facilitates cell-cell fusion of mononucleated muscle progenitor cells (MPCs), which is required for muscle repair. Here, we show that heterologous overexpression of ANO5 confers Ca(2+)-dependent phospholipid scrambling to HEK-293 cells and that scrambling is associated with the simultaneous development of a nonselective ionic current. MPCs isolated from adult Ano5 (-/-) mice exhibit defective cell fusion in culture and produce muscle fibers with significantly fewer nuclei compared with controls. This defective fusion is associated with a decrease of Ca(2+)-dependent phosphatidylserine exposure on the surface of Ano5 (-/-) MPCs and a decrease in the amplitude of Ca(2+)-dependent outwardly rectifying ionic currents. Viral introduction of ANO5 in Ano5 (-/-) MPCs restores MPC fusion competence, ANO5-dependent phospholipid scrambling, and Ca(2+)-dependent outwardly rectifying ionic currents. ANO5-rescued MPCs produce myotubes having numbers of nuclei similar to wild-type controls. These data suggest that ANO5-mediated phospholipid scrambling or ionic currents play an important role in muscle repair. |
