抑制心肌细胞的 Neddylation 会损害胚胎心脏的形态发生。

IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
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引用次数: 0

摘要

心脏的发育是一个复杂的时空过程,涉及一系列精心策划的形态发生事件,最终形成一个高效的泵器官。人们对翻译后机制如何调控心脏发育仍然知之甚少。因此,我们研究了neddylation(NEDD8与靶蛋白的连接)如何协调心脏的发生。通过Sm22αCre基因在心脏中删除Nae1来削弱neddylation,导致早期胚胎死亡。由于心肌细胞增殖减少,突变体心脏显示出小梁和致密层扩张的缺陷,这与发育中心脏的Notch信号异常有关。总之,我们的研究结果证明了neddylation在心脏发生过程中的重要作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Inhibition of cardiomyocyte neddylation impairs embryonic cardiac morphogenesis

Inhibition of cardiomyocyte neddylation impairs embryonic cardiac morphogenesis
Heart development is a complex spatiotemporal process involving a series of orchestrated morphogenic events that result in the formation of an efficient pumping organ. How posttranslational mechanisms regulate heart development remains poorly understood. Therefore, we investigate how neddylation, the attachment of NEDD8 to target proteins, coordinates cardiogenesis. Abrogation of neddylation by deleting Nae1 in the heart via Sm22αCre led to early embryonic lethality. Mutant hearts exhibited deficits in trabeculation and expansion of the compact layer due to reduced cardiomyocyte proliferation, which was linked to abnormal Notch signaling in the developing heart. Overall, our findings demonstrate an essential role for neddylation in cardiogenesis.
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来源期刊
CiteScore
10.70
自引率
0.00%
发文量
171
审稿时长
42 days
期刊介绍: The Journal of Molecular and Cellular Cardiology publishes work advancing knowledge of the mechanisms responsible for both normal and diseased cardiovascular function. To this end papers are published in all relevant areas. These include (but are not limited to): structural biology; genetics; proteomics; morphology; stem cells; molecular biology; metabolism; biophysics; bioengineering; computational modeling and systems analysis; electrophysiology; pharmacology and physiology. Papers are encouraged with both basic and translational approaches. The journal is directed not only to basic scientists but also to clinical cardiologists who wish to follow the rapidly advancing frontiers of basic knowledge of the heart and circulation.
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