Desmoplakin is important for proper cardiac cell-cell interactions.
Desmoplakin is important for proper cardiac cell-cell interactions.
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桥粒斑蛋白对于适当的心肌细胞间相互作用很重要。
DOI：
10.1017/s1431927611012359
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Baudino,TroyA
中科院分区：
文献类型：
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作者：
Bowers,StephanieLK;McFadden,WilliamA;Borg,ThomasK;Baudino,TroyA
正常的心脏功能是通过心肌细胞之间以及与细胞外基质之间的动态相互作用来维持的。这些相互作用对心脏生长和病理生理条件下的重塑非常重要。然而，这些相互作用的确切机制仍不清楚。在这项研究中，我们研究了桥粒蛋白(DSP)在心肌细胞-细胞相互作用中的重要性。心脏中的细胞间通讯需要通过称为桥粒样结构的细胞黏附连接来形成和保持细胞接触。这种复合体的主要蛋白质成分是DSP，它在连接细胞骨架网络和质膜方面发挥着作用。我们实验室先前制备了一种针对心脏成纤维细胞质膜洗涤剂可溶部分的多克隆抗体(1611)。在试图确定1611识别哪些蛋白质的过程中，我们进行了双向电泳，并确定DSP是1611识别的主要蛋白质之一。免疫沉淀研究表明，1611能够直接下拉DSP。我们还证明了1611和抗DSP抗体在整个心脏切片中共定位。最后，通过三维培养细胞-细胞相互作用实验，我们证明了1611可以抑制细胞-细胞相互作用。这些数据表明，DSP是细胞间相互作用的重要蛋白质，并影响包括细胞因子分泌在内的多种细胞功能。
Normal cardiac function is maintained through dynamic interactions of cardiac cells with each other and with the extracellular matrix. These interactions are important for remodeling during cardiac growth and pathophysiological conditions. However, the precise mechanisms of these interactions remain unclear. In this study we examined the importance of desmoplakin (DSP) in cardiac cell-cell interactions. Cell-cell communication in the heart requires the formation and preservation of cell contacts by cell adhesion junctions called desmosome-like structures. A major protein component of this complex is DSP, which plays a role in linking the cytoskeletal network to the plasma membrane. Our laboratory previously generated a polyclonal antibody (1611) against the detergent soluble fraction of cardiac fibroblast plasma membrane. In attempting to define which proteins 1611 recognizes, we performed two-dimensional electrophoresis and identified DSP as one of the major proteins recognized by 1611. Immunoprecipitation studies demonstrated that 1611 was able to directly pulldown DSP. We also demonstrate that 1611 and anti-DSP antibodies co-localize in whole heart sections. Finally, using a three-dimensionalin vitrocell-cell interaction assay, we demonstrate that 1611 can inhibit cell-cell interactions. These data indicate that DSP is an important protein for cell-cell interactions and affects a variety of cellular functions, including cytokine secretion.