Deletion of phosphatidylserine flippase β-subunit 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. The β subunit TMEM30A is indispensable for transport and proper function of P4-ATPase. Previous studies have shown that the ATP11A and TMEM30A complex is the molecular switch for myotube formation. However, the role of in skeletal muscle regeneration remains elusive. In the current study, was highly expressed in the tibialis anterior (TA) muscles of dystrophin-null ( ) mice and BaCl -induced muscle injury model mice. We generated a satellite cell (SC)-specific conditional knockout (cKO) mouse model to investigate the role of 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 BaCl -injection. Compared to the control mice, the cKO mice showed decreased Pax7 and MYH3 SCs, indicating diminished SC proliferation, 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 in skeletal muscle regeneration.