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 th...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,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 Tmem30 a in skeletal muscle regeneration.展开更多
基金supported by the National Natural Science Foundation of China(81770950,81970841)Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(2019-12M-5-032)Department of Science and Technology of Sichuan Province(21ZDYF4279,2020JDZH0026,2021JDZH0022)。
文摘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,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 Tmem30 a in skeletal muscle regeneration.