Anillin localization defect in cardiomyocyte binucleation
Anillin localization defect in cardiomyocyte binucleation
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DOI：
10.1016/j.yjmcc.2006.06.012
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发表时间：
2006-10-01
影响因子：
5
通讯作者：
Keating, Mark T.
中科院分区：
文献类型：
--
作者：
Engel, Felix B.;Schebesta, Michael;Keating, Mark T.
心脏生长在早期发育过程中通过心肌细胞增殖而增强。相比之下，出生后的心脏生长是通过增加细胞大小来实现的。出生后的心肌细胞可以进行DNA合成、有丝分裂和双核化。然而，它们失去了完成胞质分裂的能力。其基本机制尚不清楚。有人认为，收缩元件的不完全分解会抑制胞质分裂。在这里，我们表明，血清诱导的双核的结果在正常拆卸的收缩装置。相比之下，Aurora B和Anillin定位的分析表明，双核化的特征是不对称收缩、沟收缩延迟和有缺陷的中间体形成。苯胺灵在后期不能集中在皮层，而在胞质分裂期间在中间体周围显示出扩展的定位。p38抑制挽救了中间体形成缺陷。我们发现，p38积累在胞质分裂在中间体，并建议，p38活性在胞质分裂中具有调节作用。微阵列分析表明，p38抑制上调中央纺锤体的核心成分。两者合计，我们的研究结果表明，出生后的心肌细胞形成一个卵裂沟，双核与苯胺定位缺陷。(c)2006爱思唯尔公司All rights reserved.
Heart growth is augmented during early development by cardiomyocyte proliferation. In contrast, heart growth during postnatal life occurs by increasing cell size. Postnatal cardiomyocytes can undergo DNA synthesis, mitosis and binucleation. However, they lose the ability to complete cytokinesis. The underlying mechanism is poorly understood. It has been suggested that incomplete disassembly of contractile elements prohibits cytokinesis. Here, we show that serum-induced binucleation results in the normal disassembly of the contractile apparatus. In contrast, analysis of Aurora B and Anillin localization demonstrates that binucleation is characterized by asymmetric constriction, delay of furrow constriction and defective mid-body formation. Anillin fails to focus at the cortex in anaphase and shows an expanded localization around the mid-body during cytokinesis. p38 inhibition rescues the mid-body formation defect. We show that p38 accumulates during cytokinesis at the mid-body and suggest that p38 activity has a regulatory role in cytokinesis. Microarray analysis reveals that p38 inhibition upregulates core components of the central spindle. Taken together, our results demonstrate that postnatal cardiomyocytes form a cleavage furrow and that binucleation is associated with an Anillin localization defect. (c) 2006 Elsevier Inc. All rights reserved.