DIVERSITY AMONG TIGHT JUNCTIONS IN RAT-KIDNEY - GLOMERULAR SLIT DIAPHRAGMS AND ENDOTHELIAL JUNCTIONS EXPRESS ONLY ONE ISOFORM OF THE TIGHT JUNCTION PROTEIN ZO-1
DIVERSITY AMONG TIGHT JUNCTIONS IN RAT-KIDNEY - GLOMERULAR SLIT DIAPHRAGMS AND ENDOTHELIAL JUNCTIONS EXPRESS ONLY ONE ISOFORM OF THE TIGHT JUNCTION PROTEIN ZO-1
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DOI：
10.1073/pnas.89.15.7075
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发表时间：
1992-08-01
影响因子：
11.1
通讯作者：
FARQUHAR, MG
中科院分区：
文献类型：
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作者：
KURIHARA, H;ANDERSON, JM;FARQUHAR, MG
ZO-1是一种225 kDa的外周膜蛋白，存在于所有紧密连接中。最近发现它由两个不同的异构体组成，在内部存在一个被称为Motif-Alpha的80个氨基酸的结构域。为了获得有关它们的分布和潜在功能意义的信息，我们通过使用识别ZO-1异构体或更大的含有基序-α的异构体的抗体，在大鼠肾脏中定位了这两种异构体。免疫荧光染色显示肾小管上皮细胞与包膜上皮细胞紧密连接。相反，在肾小球上皮的裂隙隔膜以及肾小球和肾小管周围毛细血管内皮细胞的紧密连接中没有含有Motif-α的异构体。通过免疫印迹分析比较纯化的肾小球和肾皮质或髓质的蛋白质，证实了这种限制性亚型的表达。因此，虽然这两种亚型在典型的上皮紧密连接中都有表达，但只有一种亚型在高度专门化的裂隙隔膜和内皮连接中表达，其中细胞间隙通常是开放的，而内皮连接很容易被生理信号打开。ZO-1亚型在肾脏结构和功能不同的连接中的差异表达表明，它们可能有助于确定不同的功能特性，特别是这些细胞间连接的不稳定性。
ZO-1 is a 225-kDa peripheral membrane protein present in all tight junctions. It was recently shown to consist of two isoforms that differ in the presence of an internal 80-amino acid domain termed motif-alpha. To obtain information on their distribution and potential functional significance we have localized the two isoforms in rat kidney by using antibodies that recognize either both ZO-1 isoforms or the larger, motif-alpha-containing isoform. By immunofluorescence, staining with both antibodies was demonstrated at all tight junctions of tubular epithelial cells and the epithelial cells of Bowman's capsule. In contrast, the motif-alpha-containing isoform was absent from the slit diaphragms of the glomerular epithelium and the tight junctions of glomerular and peritubular capillary endothelial cells. This restricted isoform expression was confirmed by immunoblot analysis comparing proteins from purified glomeruli with those from kidney cortex or medulla. Thus, while both isoforms are expressed in typical epithelial tight junctions, only a single isoform, lacking motif-alpha, is expressed in the highly specialized slit diaphragms, where the intercellular spaces are normally open, and in endothelial junctions, which are readily opened by physiologic signals. The differential expression of ZO-1 isoforms in structurally and functionally distinct junctions in the kidney suggests that they may contribute to defining the variable functional properties, in particular the lability of these intercellular junctions.