The area composita of adhering junctions connecting heart muscle cells of vertebrates -: IV:: Coalescence and amalgamation of desmosomal and adhaerens junction components -: Late processes in mammalian heart development

The area composita of adhering junctions connecting heart muscle cells of vertebrates -: IV:: Coalescence and amalgamation of desmosomal and adhaerens junction components -: Late processes in mammalian heart development
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DOI:
10.1016/j.ejcb.2007.04.001
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发表时间:
2007-07-01
影响因子:
6.6
通讯作者:
Franke, Werner W.
Franke, Werner W.
中科院分区:
生物学3区
文献类型:
--
作者:
Pieperhoff, Sebastian;Franke, Werner W.

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在成年哺乳动物心脏中,心肌细胞及其末端固定的肌原纤维束通过大阵列紧密间隔甚至融合的粘附连接(AJs)连接在一起,称为“嵌入盘”(IDs)。近年来,ID复合物引起了人们的特别关注,因为人们已经清楚,几种人类遗传性心肌病是由编码ID标记蛋白的基因突变引起的,特别是一些也被称为上皮桥粒成分的基因突变。以前,我们已经表明,在成熟的心肌ID中,桥粒样连接和粘附体连接之间的组成差异基本上消失了,形成了复合杂交结构,即复合区。我们现在报告了小鼠胚胎发生和出生后生长期间心脏形成的免疫荧光和(免疫)电镜研究结果,表明具有扩展区域复合结构的id的形成是一个晚期的,主要是出生后的过程。虽然在出生之前,小而独特的桥粒和AJs是主要的ID结构,但在成熟的心脏中,越来越大的区域组合和合并的标记蛋白模式占据了大部分ID。在时间和空间上,还证明了两个连接蛋白集合的ID形成和合并模式的差异。结合在大鼠和人类心脏发育过程中的相应观察结果,我们的研究结果表明,在其他哺乳动物中,ID的拓扑发生和区域组合的形成也是发育的后期过程。我们讨论了ID和复合区域在心功能中的重要性,因此,在心肌病和可能的心肌再生过程中。(c) 2007 Elsevier GmbH版权所有。
In the adult mammalian heart, the cardiomyocytes and thus their terminally anchored myofibrillar bundles are connected by large arrays of closely spaced or even fused adhering junctions (AJs), termed "intercalated disks" (IDs). In recent years, the ID complex has attracted special attention as it has become clear that several human hereditary cardiomyopathies are caused by mutations of genes encoding ID marker proteins, in particular some that are also known as constituents of epithelial desmosomes. Previously, we have shown that in the mature myocardial ID the compositional differences between desmosome-like and adhaerens junctions are, by and large, lost and a composite hybrid structure, the area composita, is formed. We now report results from immunofluorescence and (immuno)electron microscopic studies of heart formation during mouse embryogenesis and postnatal growth and show that the formation of the IDs with extended area composita structures is a late, primarily postnatal process. While up to birth small distinct desmosomes and AJs are resolved as predominant ID structures, areae compositae of increasing sizes and merged marker protein patterns occupy most of the IDs in the mature heart. Differences in the patterns of ID formation and amalgamation of the two ensembles of junction proteins in time and space are also demonstrated. Together with corresponding observations during rat and human heart development our results indicate that ID topogenesis and area composita formation are also late developmental processes in other mammals. We discuss the importance of the ID and the areae compositae in cardiac functions and, consequently, in cardiornyopathies and possible myocardial regeneration processes. (c) 2007 Elsevier GmbH. All rights reserved.