Deletion of phosphatidylserine flippase β-subunit Tmem30a in satellite cells leads to delayed skeletal muscle regeneration

Phosphatidylserine(PS) is distributed asymmetrically in the plasma membrane of eukaryotic cells.Phosphatidylserine flippase(P4-ATPase) transports PS from the outer leaflet of the lipid bilayer to the inner leaflet of the membrane to maintain PS asymmetry.TheβsubunitTMEM30 Ais indispensable for transport and proper function of P4-ATPase. Previous studies have shown that the ATP11 A and TMEM30 A complex is the molecular switch for myotube formation. However, the role of Tmem30 a in skeletal muscle regeneration remains elusive. In the current study, Tmem30 a was highly expressed in the tibialis anterior(TA) muscles of dystrophin-null(mdx) mice and BaCl2-induced muscle injury model mice. We generated a satellite cell(SC)-specific Tmem30 a conditional knockout(cKO) mouse model to investigate the role of Tmem30 a in skeletal muscle regeneration. The regenerative ability of cKO mice was evaluated by analyzing the number and diameter of regenerated SCs after the TA muscles were injured by BaCl2-injection. Compared to the control mice, the cKO mice showed decreased Pax7~+ and MYH3~+ SCs,indicatingdiminishedSCproliferation,and decreased expression of muscular regulatory factors(MYOD and MYOG), suggesting impaired myoblast proliferation in skeletal muscle regeneration. Taken together, these results demonstrate the essential role of Tmem30 a in skeletal muscle regeneration.