Macroglobulin complement-related encodes a protein required for septate junction organization and paracellular barrier function in Drosophila
Macroglobulin complement-related encodes a protein required for septate junction organization and paracellular barrier function in Drosophila
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DOI：
10.1242/dev.102152
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发表时间：
2014-02-15
期刊：
影响因子：
4.6
通讯作者：
Ward, Robert E.
中科院分区：
文献类型：
--
作者：
Hall, Sonia;Bone, Courtney;Ward, Robert E.
极化上皮细胞作为外部环境的屏障发挥着至关重要的作用，并使器官能够形成专门的隔室以执行基本功能。屏障功能是由细胞连接介导的，细胞连接排列在细胞之间的侧质膜上，主要是脊椎动物中的紧密连接和无脊椎动物中的分隔连接（SJS）。在过去的二十年中，已经确定了20多个基因在果蝇的SJ生物发生中起作用，包括编码连接的核心结构组分的基因，如Neurexin IV，Coracle和几种claudins，以及在组装过程中促进SJ蛋白运输的蛋白质。在这里，我们表明，巨球蛋白补体相关（Mcr），一个基因先前牵连在先天免疫，在胚胎发育过程中SJ组织和功能发挥着至关重要的作用。我们发现，Mcr与其他SJ蛋白在成熟的外胚层来源的上皮细胞共定位，它显示与其他SJ蛋白SJ本地化的相互依赖性，和Mcr突变上皮细胞未能形成一个有效的细胞旁屏障。组织特异性RNA干扰进一步表明，Mcr所需的SJ组织的细胞自主。最后，我们表现出一个独特的相互依存关系之间的Mcr和Nrg SJ本地化，提供了新的见解SJ的组织。总之，这些研究表明，Mcr是上皮SJS的核心组成部分，也突出了先天免疫和上皮屏障功能之间的有趣关系。
Polarized epithelia play crucial roles as barriers to the outside environment and enable the formation of specialized compartments for organs to carry out essential functions. Barrier functions are mediated by cellular junctions that line the lateral plasma membrane between cells, principally tight junctions in vertebrates and septate junctions (SJs) in invertebrates. Over the last two decades, more than 20 genes have been identified that function in SJ biogenesis in Drosophila, including those that encode core structural components of the junction such as Neurexin IV, Coracle and several claudins, as well as proteins that facilitate the trafficking of SJ proteins during their assembly. Here we demonstrate that Macroglobulin complement-related (Mcr), a gene previously implicated in innate immunity, plays an essential role during embryonic development in SJ organization and function. We show that Mcr colocalizes with other SJ proteins in mature ectodermally derived epithelial cells, that it shows interdependence with other SJ proteins for SJ localization, and that Mcr mutant epithelia fail to form an effective paracellular barrier. Tissue-specific RNA interference further demonstrates that Mcr is required cell-autonomously for SJ organization. Finally, we show a unique interdependence between Mcr and Nrg for SJ localization that provides new insights into the organization of the SJ. Together, these studies demonstrate that Mcr is a core component of epithelial SJs and also highlight an interesting relationship between innate immunity and epithelial barrier functions.