Interspecies conservation and differential expression of mouse desmoglein gene family

Interspecies conservation and differential expression of mouse desmoglein gene family
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DOI:
10.1034/j.1600-0625.2002.110203.x
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发表时间:
2002-04-01
影响因子:
3.6
通讯作者:
Pulkkinen, L
Pulkkinen, L
中科院分区:
医学2区
文献类型:
--
作者:
Mahoney, MG;Simpson, A;Pulkkinen, L

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上皮细胞粘附是由细胞间连接,称为桥粒介导。桥粒芯糖蛋白(Dsg; Dsg 1、Dsg 2和Dsg 3)是桥粒的钙依赖性跨膜粘附组分。虽然Dsg 1和Dsg 3主要限于复层鳞状上皮,但Dsg 2基本上在所有含桥粒的上皮中表达。在表皮中,Dsg 2和Dsg 3在基底角质形成细胞中表达,而Dsg 1在整个上分化细胞层中表达。迄今为止,在小鼠中,仅Dsg 3已通过分子克隆表征。在这项研究中,我们已经克隆和表征小鼠Dsg 1和Dsg 2基因。小鼠Dsg 1全长cDNA(5.5 kb)含有一个3171 bp的开放阅读框(ORF),编码1057个氨基酸的前体蛋白。Dsg 2 cDNA(6.3kb)具有3366 bp的开放阅读框,编码1122个氨基酸的前体蛋白。小鼠Dsg 2蛋白与人DSG 2具有76%的同一性,但与小鼠Dsg 1和Dsg 3分别仅具有26%和33%的同一性。桥粒芯糖蛋白基因的内含子/外显子组织的分析显示显着的保守性。然而,这些桥粒芯糖蛋白的mRNA表达模式在小鼠胚胎发育过程中,并在各种成人组织是可变的。虽然Dsg 2和Dsg 3在所有发育阶段都表达,但Dsg 1的表达延迟至小鼠胚胎的第15天。在成年小鼠组织中,Dsg 2广泛表达,而Dsg 1和Dsg 3的表达仅限于选定的组织。总之,虽然桥粒芯糖蛋白在基因和蛋白质水平上都具有高度同源性,但它们的表达在空间和时间上受到调节,这可能有助于它们在发育过程中在细胞-细胞粘附中发挥重要作用。
Epithelial cell adhesion is mediated by intercellular junctions, called desmosomes. Desmogleins (Dsg; Dsg1, Dsg2 and Dsg3) are calcium-dependent transmembrane adhesion components of the desmosomes. While Dsg1 and Dsg3 are mainly restricted to stratified squamous epithelia, Dsg2 is expressed in essentially all desmosome-containing epithelia. In the epidermis, Dsg2 and Dsg3 are expressed in the basal keratinocytes while Dsg1 is expressed throughout the upper differentiating cell layers. To date, in mouse, only Dsg3 has been characterized by molecular cloning. In this study, we have cloned and characterized the mouse Dsg1 and Dsg2 genes. The full-length mouse Dsg1 cDNA (5.5 kb) contains an open reading frame (ORF) of 3171 bp encoding a precursor protein of 1057 amino acids. The Dsg2 cDNA (6.3 kb) has an ORF of 3366 bp coding for a precursor protein of 1122 amino acids. Mouse Dsg2 protein shares 76% identity with human DSG2 but only 26% and 33% identity with mouse Dsg1 and Dsg3, respectively. Analysis of intron/exon organization of the desmoglein genes revealed significant conservation. However, the mRNA expression patterns of these desmogleins during mouse embryonic development and in various adult tissues are variable. While Dsg2 and Dsg3 are expressed in all developmental stages, Dsg1 expression is delayed until day 15 of mouse embryos. In adult mouse tissues, Dsg2 is widely expressed while the expression of Dsg1 and Dsg3 is restricted to select tissues. In summary, while desmogleins share high homology at both the gene and protein level, their expression is spatially and temporally regulated, potentially contributing to their significant role in cell-cell adhesion during development.