Division of Cell Biology, Department of Physiology and Cell Biology, Graduate School of Medicine, Kobe University, Kobe 650-0017, Japan.
Biochem Biophys Res Commun. 2011 Sep 23;413(2):224-9. doi: 10.1016/j.bbrc.2011.08.073. Epub 2011 Aug 22.
Cell-cell junctions 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 ∼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.
细胞-细胞连接在上皮细胞和内皮细胞片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 KIAA1462 基因的蛋白质产物，其单核苷酸多态性（SNP）最近被报道与冠状动脉疾病相关，是细胞-细胞连接的一个新组成部分。我们提出了与冠状动脉疾病相关的 KIAA1462 蛋白连接蛋白（JCAD）的名称。JCAD 是一种约 145kDa 的蛋白质，没有任何已知的结构域，但含有一个富含脯氨酸的区域。免疫定位研究表明，JCAD特异性定位于内皮细胞的细胞-细胞连接处，但不在上皮细胞中。用 RNAi 介导的 VE-钙粘蛋白表达抑制可削弱 JCAD 在培养的内皮细胞中在细胞-细胞连接处的积累。在细胞黏附缺陷型小鼠 L 成纤维细胞中，当诱导钙粘蛋白介导的细胞-细胞黏附时，JCAD 被募集到细胞-细胞接触处。这些结果表明 JCAD 是内皮细胞中基于 VE-钙粘蛋白的细胞-细胞连接的一个组成部分。本研究还提示内皮细胞-细胞黏附在冠状动脉疾病中的重要性。
