Requirement of plakophilin 2 for heart morphogenesis and cardiac junction formation.
Requirement of plakophilin 2 for heart morphogenesis and cardiac junction formation.
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plakophilin 2对心形形态发生和心脏连接形成的需求。
DOI：
10.1083/jcb.200402096
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发表时间：
2004-10-11
影响因子：
7.8
通讯作者：
Birchmeier, Walter
中科院分区：
文献类型：
--
作者：
Grossmann, Katja S;Grund, Christine;Huelsken, Joerg;Behrend, Martin;Erdmann, Bettina;Franke, Werner W;Birchmeier, Walter
原虫蛋白是一种在胚胎发育和成体发育中起作用的螳螂家族的蛋白质，当突变时会导致疾病。我们已经在小鼠身上去除了血小板亲和素2基因。由此产生的突变小鼠在怀孕中期(E10.5-E11)表现出心脏形态发生和稳定性的致命变化，特征是小梁减少，细胞骨架分散，心壁破裂，血液渗入心包腔。在没有Plakopin2的情况下，细胞骨架连接蛋白Desmoplakin从连接心肌细胞的黏附连接的斑块中解离，并在细胞质中形成颗粒状聚集体。相比之下，胚胎上皮细胞呈现正常的连接。因此，我们得出结论，血小板亲和素2对于连接蛋白的组装是重要的，并且是心脏的一个重要的形态发生因子和结构成分。
Plakophilins are proteins of the armadillo family that function in embryonic development and in the adult, and when mutated can cause disease. We have ablated the plakophilin 2 gene in mice. The resulting mutant mice exhibit lethal alterations in heart morphogenesis and stability at mid-gestation (E10.5–E11), characterized by reduced trabeculation, disarrayed cytoskeleton, ruptures of cardiac walls, and blood leakage into the pericardiac cavity. In the absence of plakophilin 2, the cytoskeletal linker protein desmoplakin dissociates from the plaques of the adhering junctions that connect the cardiomyocytes and forms granular aggregates in the cytoplasm. By contrast, embryonic epithelia show normal junctions. Thus, we conclude that plakophilin 2 is important for the assembly of junctional proteins and represents an essential morphogenic factor and architectural component of the heart.