The fat-like gene of Drosophila is the true orthologue of vertebrate fat cadherins and is involved in the formation of tubular organs
The fat-like gene of Drosophila is the true orthologue of vertebrate fat cadherins and is involved in the formation of tubular organs
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DOI：
10.1074/jbc.m313878200
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发表时间：
2004-06-04
影响因子：
4.8
通讯作者：
Baumgartner, S
中科院分区：
文献类型：
--
作者：
Castillejo-López, C;Arias, WM;Baumgartner, S
脂肪钙粘蛋白构成钙粘蛋白大家族的一个亚类，其特征是存在34个钙粘蛋白基序。到目前为止，已经描述了三种哺乳动物脂肪钙粘蛋白;然而，关于这些分子的功能，只有有限的信息是已知的。在本文中，我们描述了果蝇的第二脂肪钙粘蛋白，脂肪样（FTL）。我们发现，ftl是真正的直向同源的脊椎动物脂肪样基因，而以前的特点，肿瘤抑制钙粘蛋白，脂肪，是更远的关系相比，ftl。Ftl是4705个氨基酸的大分子。它在管腔组织如气管、唾液腺、前胃和后肠的顶端表达。ftl沉默导致气管上皮细胞塌陷，产生断裂、缺失和囊样结构。其他管状器官如前胃、唾液腺和后肠也畸形或缺失。这些数据表明，Ftl是必需的外胚层来源的管状结构的形态发生和维护，并强调其功能的相似性，以报告的致死小鼠敲除脂肪1肾小球上皮过程崩溃。基于我们的研究结果，我们提出了一个模型，其中Ftl作为间隔保持肾小管上皮细胞分开，而不是先前描述的粘附特性的钙粘蛋白超家族。
Fat cadherins constitute a subclass of the large cadherin family characterized by the presence of 34 cadherin motifs. To date, three mammalian Fat cadherins have been described; however, only limited information is known about the function of these molecules. In this paper, we describe the second fat cadherin in Drosophila, fat-like (ftl). We show that ftl is the true orthologue of vertebrate fat-like genes, whereas the previously characterized tumor suppressor cadherin, fat, is more distantly related as compared with ftl. Ftl is a large molecule of 4705 amino acids. It is expressed apically in luminal tissues such as trachea, salivary glands, proventriculus, and hindgut. Silencing of ftl results in the collapse of tracheal epithelia giving rise to breaks, deletions, and sac-like structures. Other tubular organs such as proventriculus, salivary glands, and hindgut are also malformed or missing. These data suggest that Ftl is required for morphogenesis and maintenance of tubular structures of ectodermal origin and underline its similarity in function to a reported lethal mouse knock-out of fat1 where glomerular epithelial processes collapse. Based on our results, we propose a model where Ftl acts as a spacer to keep tubular epithelia apart rather than the previously described adhesive properties of the cadherin superfamily.