A coronary artery disease-associated gene product, JCAD/KIAA1462, is a novel component of endothelial cell-cell junctions
A coronary artery disease-associated gene product, JCAD/KIAA1462, is a novel component of endothelial cell-cell junctions
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DOI：
10.1016/j.bbrc.2011.08.073
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发表时间：
2011-09-23
影响因子：
3.1
通讯作者：
Furuse, Mikio
中科院分区：
文献类型：
--
作者：
Akashi, Masaya;Higashi, Tomohito;Furuse, Mikio
细胞间连接在上皮和内皮细胞层的组织和功能中起着至关重要的作用。在这里，我们已经确定了KIAA 1462基因的蛋白质产物，其单核苷酸多态性（SNPs）最近被报道与冠状动脉疾病相关，作为细胞-细胞连接的新成分。我们建议将KIAA 1462蛋白命名为与冠状动脉疾病相关的连接蛋白（JCAD）。JCAD是一种类似于145 kDa的蛋白质，没有任何已知的结构域，但含有富含脯氨酸的区域。免疫定位研究表明，JCAD是专门定位在内皮细胞，但不是在上皮细胞的细胞-细胞连接。RNAi介导的VE-钙粘蛋白表达的抑制损害了JCAD在培养的内皮细胞中细胞-细胞连接处的积累。在细胞粘附缺陷的小鼠L成纤维细胞中，当钙粘蛋白介导的细胞-细胞粘附被诱导时，JCAD被招募到细胞-细胞接触中。这些结果表明，JCAD是内皮细胞中基于VE-钙粘蛋白的细胞-细胞连接的组分。这项研究还表明内皮细胞-细胞粘附在冠状动脉疾病中的意义。(C)2011 Elsevier Inc. All rights reserved.
Cell-cell junctioris play crucial roles in the organization and function of epithelial and endothelial cellular sheets. Here, we have identified the protein product for KIAA1462 gene, whose single nucleotide polymorphisms (SNPs) have recently reported to be associated with coronary artery disease, as a novel component of cell-cell junctions. We propose the name of KIAA1462 protein junctional protein associated with coronary artery disease (JCAD). JCAD is a similar to 145 kDa protein without any known domains but contains a proline-rich region. Immunolocalization studies revealed that JCAD is specifically localized at cell-cell junctions in endothelial cells but not in epithelial cells. The accumulation of JCAD at cell-cell junctions in cultured endothelial cells was impaired by RNAi-mediated suppression of VE-cadherin expression. In cell adhesion-deficient mouse L fibroblasts, JCAD was recruited to cell-cell contacts when cadherin-mediated cell-cell adhesion was induced. These results indicate that JCAD is a component of VE-cadherin-based cell-cell junctions in endothelial cells. This study also suggests the implication of endothelial cell-cell adhesion in coronary artery disease. (C) 2011 Elsevier Inc. All rights reserved.