Dynamic Alterations to α-Actinin Accompanying Sarcomere Disassembly and Reassembly during Cardiomyocyte Mitosis.
Dynamic Alterations to α-Actinin Accompanying Sarcomere Disassembly and Reassembly during Cardiomyocyte Mitosis.
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DOI：
10.1371/journal.pone.0129176
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Schulz R
中科院分区：
文献类型：
--
作者：
Fan X;Hughes BG;Ali MA;Cho WJ;Lopez W;Schulz R
尽管哺乳动物被认为在出生后不久就失去了再生心肌的能力，但哺乳动物的胚胎和新生儿心肌细胞是增生性的。在增殖过程中，这些细胞需要选择性地分解其肌原纤维以成功进行细胞分裂。然而，肌节分解的机制尚不清楚。为了研究这一点，我们对增殖的新生大鼠心室肌细胞中的多种肉瘤蛋白进行了一系列免疫荧光研究，并将这些观察结果与不同细胞周期阶段的生化变化联系起来。在肌细胞有丝分裂过程中，α-肌动蛋白和肌动蛋白早在前期就被分解。α-肌动蛋白（代表肌动蛋白z -盘）的分解先于肌动蛋白（m -线）的分解，表明肌动蛋白的分解发生在z -盘的坍塌之后。肌节的分解与核膜的溶解同时发生。几种细胞内蛋白酶抑制剂不能阻断α-肌动蛋白或肌动蛋白的分解。在有丝分裂过程中，胞浆α-肌动蛋白（可溶性）和肌聚体α-肌动蛋白均显著增加，胞浆α-肌动蛋白的磷酸化水平低于肌聚体α-肌动蛋白。细胞周期蛋白依赖性激酶1 （CDK1）的抑制诱导肌节的快速重组。心肌细胞有丝分裂中肌节的分裂和重组依赖于cdk1，并且具有肌聚体和细胞质α-肌动蛋白翻译后的动态差异修饰。
Although mammals are thought to lose their capacity to regenerate heart muscle shortly after birth, embryonic and neonatal cardiomyocytes in mammals are hyperplastic. During proliferation these cells need to selectively disassemble their myofibrils for successful cytokinesis. The mechanism of sarcomere disassembly is, however, not understood. To study this, we performed a series of immunofluorescence studies of multiple sarcomeric proteins in proliferating neonatal rat ventricular myocytes and correlated these observations with biochemical changes at different cell cycle stages. During myocyte mitosis, α-actinin and titin were disassembled as early as prometaphase. α-actinin (representing the sarcomeric Z-disk) disassembly precedes that of titin (M-line), suggesting that titin disassembly occurs secondary to the collapse of the Z-disk. Sarcomere disassembly was concurrent with the dissolution of the nuclear envelope. Inhibitors of several intracellular proteases could not block the disassembly of α-actinin or titin. There was a dramatic increase in both cytosolic (soluble) and sarcomeric α-actinin during mitosis, and cytosolic α-actinin exhibited decreased phosphorylation compared to sarcomeric α-actinin. Inhibition of cyclin-dependent kinase 1 (CDK1) induced the quick reassembly of the sarcomere. Sarcomere dis- and re-assembly in cardiomyocyte mitosis is CDK1-dependent and features dynamic differential post-translational modifications of sarcomeric and cytosolic α-actinin.
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影响因子：
37.8
作者：
Ali MA;Cho WJ;Hudson B;Kassiri Z;Granzier H;Schulz R
通讯作者：
Schulz R
影响因子：
64.5
作者：
Huttlin EL;Jedrychowski MP;Elias JE;Goswami T;Rad R;Beausoleil SA;Villén J;Haas W;Sowa ME;Gygi SP
通讯作者：
Gygi SP
影响因子：
14.9
作者：
Hornbeck PV;Kornhauser JM;Tkachev S;Zhang B;Skrzypek E;Murray B;Latham V;Sullivan M
通讯作者：
Sullivan M
影响因子：
10.8
作者：
Kandasamy, Arulmozhi D.;Schulz, Richard
通讯作者：
Schulz, Richard
影响因子：
4.3
作者：
Barta, J;Tóth, A;Papp, Z
通讯作者：
Papp, Z