THE DROSOPHILA-MELANOGASTER FLIGHTLESS-I GENE INVOLVED IN GASTRULATION AND MUSCLE DEGENERATION ENCODES GELSOLIN-LIKE AND LEUCINE-RICH REPEAT DOMAINS AND IS CONSERVED IN CAENORHABDITIS-ELEGANS AND HUMANS
THE DROSOPHILA-MELANOGASTER FLIGHTLESS-I GENE INVOLVED IN GASTRULATION AND MUSCLE DEGENERATION ENCODES GELSOLIN-LIKE AND LEUCINE-RICH REPEAT DOMAINS AND IS CONSERVED IN CAENORHABDITIS-ELEGANS AND HUMANS
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DOI：
10.1073/pnas.90.23.11386
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发表时间：
1993-12-01
影响因子：
11.1
通讯作者：
MIKLOS, GLG
中科院分区：
文献类型：
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作者：
CAMPBELL, HD;SCHIMANSKY, T;MIKLOS, GLG
果蝇flightless-I基因座（fliI）的突变会导致果蝇在早期胚胎发生过程中不能飞行，或者严重时导致细胞化不完全，随后导致中胚层内陷和原肠胚形成异常。经过染色体步移、缺陷作图和转基因分析，我们分离并鉴定了flightless-I cDNA，从而能够预测1256个残基的蛋白质的完整氨基酸序列。数据库搜索发现一个同源基因秀丽隐杆线虫，我们已经分离和鉴定相应的cDNA。根据C. elegans和D.我们克隆了一个人的同源cDNA。预测的C. elegans和人的蛋白质分别与D.黑胃蛋白预测的蛋白质具有显着的序列相似性肌动蛋白结合蛋白凝溶胶蛋白和相关蛋白质，此外，有一个N-末端结构域组成的重复的两亲性亮氨酸丰富的基序。这个重复在D中找到。黑腹酵母、酿酒酵母和已知参与细胞粘附和与其它蛋白质结合的哺乳动物蛋白质。母体表达的flightless-I蛋白的结构表明，它可能通过与细胞骨架和其他细胞成分相互作用在胚胎细胞化中发挥关键作用。在线虫、蝇和人类中存在高度保守的同源物，表明这种蛋白质在许多后生动物中具有重要作用。
Mutations at the flightless-I locus (fliI) of Drosophila melanogaster cause flightlessness or, when severe, incomplete cellularization during early embryogenesis, with subsequent abnormalities in mesoderm invagination and in gastrulation. After chromosome walking, deficiency mapping, and transgenic analysis, we have isolated and characterized flightless-I cDNAs, enabling prediction of the complete amino acid sequence of the 1256-residue protein. Data base searches revealed a homologous gene in Caenorhabditis elegans, and we have isolated and characterized corresponding cDNAs. By using the polymerase chain reaction with nested sets of degenerate oligonucleotide primers based on conserved regions of the C. elegans and D. melanogaster proteins, we have cloned a homologous human cDNA. The predicted C. elegans and human proteins are, respectively, 49% and 58% identical to the D. melanogaster protein. The predicted proteins have significant sequence similarity to the actin-binding protein gelsolin and related proteins and, in addition, have an N-terminal domain consisting of a repetitive amphipathic leucine-rich motif. This repeat is found in D. melanogaster, Saccharomyces cerevisiae, and mammalian proteins known to be involved in cell adhesion and in binding to other proteins. The structure of the maternally expressed flightless-I protein suggests that it may play a key role in embryonic cellularization by interacting with both the cytoskeleton and other cellular components. The presence of a highly conserved homologue in nematodes, flies, and humans is indicative of a fundamental role for this protein in many metazoans.