Arginyltransferase regulates alpha cardiac actin function, myofibril formation and contractility during heart development.
Arginyltransferase regulates alpha cardiac actin function, myofibril formation and contractility during heart development.
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DOI：
10.1242/dev.022723
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发表时间：
2008-12
期刊：
影响因子：
--
通讯作者：
Kashina A
中科院分区：
文献类型：
--
作者：
Rai R;Wong CC;Xu T;Leu NA;Dong DW;Guo C;McLaughlin KJ;Yates JR 3rd;Kashina A
精氨酰转移酶 (Ate1) 介导的翻译后精氨酰化对于哺乳动物的心血管发育和血管生成至关重要，并直接影响发育中心脏的心肌结构。我们最近表明，精氨酸化通过修饰参与肌动蛋白细胞骨架功能和细胞运动事件的蛋白质来发挥许多细胞内效应。在这里，我们研究精氨酸化在胚胎发生过程中心肌细胞及其含肌动蛋白结构的发育和功能中的作用。生化和质谱分析表明，α 心脏肌动蛋白在发育过程中在多个位点发生精氨酰化。对野生型和 Ate1 敲除小鼠心脏中肌原纤维的超微结构分析表明，精氨酸化的缺失会导致肌原纤维结构缺陷，从而延迟其发育并影响整个心脏中肌原纤维的连续性，从而预测心肌收缩力的缺陷。来自野生型和 Ate1 敲除小鼠胚胎的心肌细胞的比较表明，精氨酸化的缺失会导致异常的跳动模式。我们的结果表明，精氨酰化敲除小鼠的细胞自主心肌细胞缺陷会导致与人类疾病中观察到的严重先天性异常相似，并概述了精氨酰化在调节心肌细胞肌动蛋白细胞骨架中的新功能。
Posttranslational arginylation mediated by arginyltransferase (Ate1) is essential for cardiovascular development and angiogenesis in mammals and directly affects the myocardium structure in the developing heart. We recently showed that arginylation exerts a number of intracellular effects by modifying proteins involved in the functioning of actin cytoskeleton and the events of cell motility. Here we investigate the role of arginylation in the development and function of cardiac myocytes and their actin-containing structures during embryogenesis. Biochemical and mass spectrometry analysis shows that alpha cardiac actin undergoes arginylation on multiple sites during development. Ultrastructural analysis of the myofibrils in wild type and Ate1 knockout mouse hearts shows that the absence of arginylation results in defects in myofibril structure that delay their development and affect the continuity of myofibrils throughout the heart, predicting defects in cardiac contractility. Comparison of cardiac myocytes derived from wild type and Ate1 knockout mouse embryos show that the absence of arginylation results in abnormal beating patterns. Our results demonstrate cell-autonomous cardiac myocyte defects in arginylation knockout mice that lead to severe congenital abnormalities similar to those observed in human disease, and outline a new function of arginylation in the regulation of actin cytoskeleton in cardiac myocytes.
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影响因子：
4
作者：
OTEY, CA;KALNOSKI, MH;BULINSKI, JC
通讯作者：
BULINSKI, JC
影响因子：
--
作者：
OTEY, CA;KALNOSKI, MH;BULINSKI, JC
通讯作者：
BULINSKI, JC
影响因子：
56.9
作者：
Otterbein, LR;Graceffa, P;Dominguez, R
通讯作者：
Dominguez, R
影响因子：
4.8
作者：
Eriste, E;Norberg, Å;Sillard, R
通讯作者：
Sillard, R
影响因子：
4.8
作者：
Conti, MA;Even-Ram, S;Adelstein, RS
通讯作者：
Adelstein, RS