Drosophila coracle, a member of the protein 4.1 superfamily, has essential structural functions in the septate junctions and developmental functions in embryonic and adult epithelial cells

Drosophila coracle, a member of the protein 4.1 superfamily, has essential structural functions in the septate junctions and developmental functions in embryonic and adult epithelial cells
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DOI:
10.1091/mbc.9.12.3505
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发表时间:
1998-12-01
影响因子:
3.3
通讯作者:
Fehon, RG
Fehon, RG
中科院分区:
生物学3区
文献类型:
--
作者:
Lamb, RS;Ward, RE;Fehon, RG

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尽管对蛋白质4.1超家族的生物化学进行了广泛的研究,但在遗传学方面还没有得到很好的描述。对一种果蝇蛋白4.1同源物Coracle的研究,为研究该基因家族的遗传功能提供了机会。Corail最初被认为是EGFR(ELP)的显性抑制因子,EGFR是果蝇表皮生长因子受体基因的一种多态形式。在这篇文章中,我们提出了一种新的表型分析方法,这是第一次对蛋白质4.1超家族成员进行表型分析。对新的喙等位基因的筛查证实了胚胎致死性和背部闭合失败的喙零表型,并确定了胚胎表皮和唾液腺的额外缺陷。亚形冠状等位基因在许多想象的组织中显示出功能。对Coracle突变细胞的分析表明,Coracle是维持跨上皮屏障所需的间隔连接的必要结构成分,但对于顶端-基底极性、上皮完整性或细胞骨架完整性来说不是必需的。此外,冠状突起的表型表明在细胞信号事件中有特定的作用。最后,互补分析提供了关于Coracle和其他可能的蛋白质4.1超家族成员的功能组织的信息。这些研究为Coracle在发育中的胚胎和成人体内的一系列功能提供了洞察力。
Although extensively studied biochemically, members of the Protein 4.1 superfamily have not been as well characterized genetically. Studies of coracle, a Drosophila Protein 4.1 homologue, provide an opportunity to examine the genetic functions of this gene family. coracle was originally identified as a dominant suppressor of Egfr(Elp), a hypermorphic form of the Drosophila Epidermal growth factor receptor gene. In this article, we present a phenotypic analysis of coracle, one of the first for a member of the Protein 4.1 superfamily. Screens for new coracle alleles confirm the null coracle phenotype of embryonic lethality and failure in dorsal closure, and they identify additional defects in the embryonic epidermis and salivary glands. Hypomorphic coracle alleles reveal functions in many imaginal tissues. Analysis of coracle mutant cells indicates that Coracle is a necessary structural component of the septate junction required for the maintenance of the transepithelial barrier but is not necessary for apical-basal polarity, epithelial integrity, or cytoskeletal integrity. In addition, coracle phenotypes suggest a specific role in cell signaling events. Finally, complementation analysis provides information regarding the functional organization of Coracle and possibly other Protein 4.1 superfamily members. These studies provide insights into a range of in vivo functions for coracle in developing embryos and adults.