Castillejo-López Casimiro, Arias Wilma Martinez, Baumgartner Stefan
Department of Cell and Molecular Biology, Lund University, BMC B13, S-22184 Lund, Sweden.
J Biol Chem. 2004 Jun 4;279(23):24034-43. doi: 10.1074/jbc.M313878200. Epub 2004 Mar 26.
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.
FAT钙黏蛋白构成了大型钙黏蛋白家族的一个亚类，其特征是存在34个钙黏蛋白基序。迄今为止，已描述了三种哺乳动物FAT钙黏蛋白；然而，关于这些分子的功能，已知信息有限。在本文中，我们描述了果蝇中的第二种FAT钙黏蛋白，类FAT（ftl）。我们表明，ftl是脊椎动物类FAT基因的真正直系同源物，而先前表征的肿瘤抑制钙黏蛋白FAT与ftl的亲缘关系更远。Ftl是一个由4705个氨基酸组成的大分子。它在气管、唾液腺、前胃和后肠等腔组织的顶端表达。ftl的沉默导致气管上皮细胞塌陷，产生断裂、缺失和囊状结构。其他管状器官，如前胃、唾液腺和后肠，也会出现畸形或缺失。这些数据表明，Ftl是外胚层来源的管状结构形态发生和维持所必需的，并强调了其功能与报道的fat1致死性小鼠敲除相似，在该敲除中肾小球上皮突起塌陷。基于我们的结果，我们提出了一个模型，其中Ftl作为一个间隔物，使管状上皮细胞分开，而不是先前描述的钙黏蛋白超家族的黏附特性。
