Whittaker C A, Desimone D W
Department of Cell Biology, University of Virginia, Charlottesville 22908, USA.
Ann N Y Acad Sci. 1998 Oct 23;857:56-73. doi: 10.1111/j.1749-6632.1998.tb10107.x.
Integrin receptors containing an alpha 4 subunit mediate cell-cell adhesion by binding to VCAM and MadCAM-1 in addition to supporting cell-extracellular matrix (ECM) adhesion by binding to the alternatively spliced V-region of fibronectin (FN). Studies in chick and mouse embryos have implicated these integrins in neural crest migration, myotube formation, heart development, and placentation. Because integrin-FN adhesive interactions have been shown to play essential roles in mammalian development, studies were initiated of integrin alpha 4 in amphibian embryos, which are better suited to experimental analyses of the earliest stages of embryogenesis. Here, the cDNA cloning and pattern of expression of the Xenopus laevis homolog of integrin alpha 4 is reported. Xenopus alpha 4 is 55% identical at the amino-acid level to both its human and mouse counterparts, including conservation of an alpha 4-specific protease cleavage site, 11 potential N-linked glycosylation sites, and 24 cysteine residues. In situ hybridization analysis reveals that transcripts encoding alpha 4 are expressed in epidermis and the branchial arches. Although alpha 4 transcripts can be detected as early as gastrulation, the protein is observed only after tailbud stages of development and is spatially restricted to the epidermis and gills of tadpole stage embryos. From these data it is concluded that Xenopus integrin alpha 4 has structural features in common with other vertebrate alpha 4 homologs, but is detected in a more restricted tissue distribution during development than alpha 4 in other species.
含有α4亚基的整合素受体，除了通过与纤连蛋白（FN）可变剪接的V区域结合来支持细胞与细胞外基质（ECM）的黏附外，还通过与血管细胞黏附分子（VCAM）和黏膜地址素细胞黏附分子-1（MadCAM-1）结合来介导细胞间黏附。对鸡和小鼠胚胎的研究表明，这些整合素参与神经嵴迁移、肌管形成、心脏发育和胎盘形成。由于整合素与FN的黏附相互作用已被证明在哺乳动物发育中起重要作用，因此对两栖类胚胎中的整合素α4展开了研究，两栖类胚胎更适合对胚胎发育最早阶段进行实验分析。在此，报道了非洲爪蟾整合素α4同源物的cDNA克隆及表达模式。非洲爪蟾α4在氨基酸水平上与其人类和小鼠对应物的相似度为55%，包括一个α4特异性蛋白酶切割位点、11个潜在的N-连接糖基化位点和24个半胱氨酸残基的保守性。原位杂交分析显示，编码α4的转录本在表皮和鳃弓中表达。尽管早在原肠胚形成期就能检测到α4转录本，但该蛋白仅在发育的尾芽期后才被观察到，并且在空间上局限于蝌蚪期胚胎的表皮和鳃。从这些数据可以得出结论，非洲爪蟾整合素α4与其他脊椎动物α4同源物具有共同的结构特征，但在发育过程中其组织分布比其他物种的α4更受限。
