Deletion of phosphatidylserine flippase β-subunit Tmem30a in satellite cells leads to delayed skeletal muscle regeneration.
Deletion of phosphatidylserine flippase β-subunit Tmem30a in satellite cells leads to delayed skeletal muscle regeneration.
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卫星细胞中磷脂酰丝氨酸翻转酶β亚基Tmem30a的缺失导致骨骼肌再生延迟
DOI：
10.24272/j.issn.2095-8137.2021.195
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发表时间：
2021-09-18
影响因子：
4.9
通讯作者：
Zhu XJ
中科院分区：
文献类型：
--
作者：
Sun KX;Jiang XY;Li X;Su YJ;Wang JL;Zhang L;Yang YM;Zhu XJ
磷脂酰丝氨酸（PS）在真核细胞的质膜中不对称分布。磷脂酰丝氨酸翻转酶（p4 - atp酶）将磷脂酰丝氨酸从脂质双分子层的外小叶转运到膜的内小叶，维持磷脂酰丝氨酸的不对称性。β亚基TMEM30A对于p4 - atp酶的转运和正常功能是必不可少的。先前的研究表明，ATP11A和TMEM30A复合物是肌管形成的分子开关。然而，Tmem30a在骨骼肌再生中的作用尚不明确。在本研究中，Tmem30a在肌营养不良蛋白缺失（mdx）小鼠和bacl2诱导的肌肉损伤模型小鼠的胫骨前肌（TA）中高表达。我们建立了卫星细胞（SC）特异性Tmem30a条件敲除（cKO）小鼠模型，以研究Tmem30a在骨骼肌再生中的作用。通过分析注射bacl2损伤TA肌肉后再生SCs的数量和直径，评价cKO小鼠的再生能力。与对照组小鼠相比，cKO小鼠Pax7+和MYH3+ SCs减少，表明SC增殖减少，肌肉调节因子（MYOD和MYOG）表达减少，表明骨骼肌再生中成肌细胞增殖受损。综上所述，这些结果证明了Tmem30a在骨骼肌再生中的重要作用。
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 Tmem30a in skeletal muscle regeneration remains elusive. In the current study, Tmem30a 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 Tmem30a conditional knockout (cKO) mouse model to investigate the role of Tmem30a 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 Tmem30a in skeletal muscle regeneration.
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DOI：
10.1083/jcb.200508001
发表时间：
2006-01-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kuang S;Chargé SB;Seale P;Huh M;Rudnicki MA
通讯作者：
Rudnicki MA
影响因子：
56.9
作者：
Gurevich, David B.;Phong Dang Nguyen;Currie, Peter D.
通讯作者：
Currie, Peter D.
影响因子：
4.8
作者：
Bryde, Susanne;Hennrich, Hanka;Holthuis, Joost C. M.
通讯作者：
Holthuis, Joost C. M.
影响因子：
4.3
作者：
Liu W;Peng L;Tian W;Li Y;Zhang P;Sun K;Yang Y;Li X;Li G;Zhu X
通讯作者：
Zhu X
影响因子：
82.9
作者：
Dumont NA;Wang YX;von Maltzahn J;Pasut A;Bentzinger CF;Brun CE;Rudnicki MA
通讯作者：
Rudnicki MA