A tetraspanin regulates septate junction formation in Drosophila midgut
A tetraspanin regulates septate junction formation in Drosophila midgut
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DOI：
10.1242/jcs.180448
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发表时间：
2016-03-15
影响因子：
4
通讯作者：
Furuse, Mikio
中科院分区：
文献类型：
--
作者：
Izumi, Yasushi;Motoishi, Minako;Furuse, Mikio
隔膜连接（SJS）是无脊椎动物上皮细胞中限制溶质通过细胞旁途径自由扩散的膜特化。在节肢动物中，观察到两种形态学上不同类型的分隔连接;褶状（PSJ）和光滑（SSJ），其分别存在于外胚层和内胚层来源的上皮中。最近在果蝇中鉴定的sSJ特异性蛋白，Mesh和Ssk，表明sSJs和pSJs的分子组成不同。一个缺陷筛选的基础上免疫定位网确定了四跨膜蛋白家族蛋白，Tsp 2A，作为一个新发现的蛋白质参与sSJ形成果蝇。Tsp 2A特异性定位于中肠和马氏管中的sSJS。CRISPR/Cas9系统RNA导致的Tsp 2A表达受损与sSJ超微结构缺陷、其他sSJ蛋白定位改变以及中肠屏障功能受损有关。在大多数Tsp 2A突变细胞中，Mesh未能定位于sSJS，而是分布于细胞质中。Tsp 2A与Mesh和Ssk形成复合物，并且这些蛋白质对于它们的定位相互依赖。这些观察表明Tsp 2A与Mesh和Ssk合作组织sSJS。
Septate junctions (SJs) are membrane specializations that restrict the free diffusion of solutes through the paracellular pathway in invertebrate epithelia. In arthropods, two morphologically different types of septate junctions are observed; pleated (pSJs) and smooth (sSJs), which are present in ectodermally and endodermally derived epithelia, respectively. Recent identification of sSJ-specific proteins, Mesh and Ssk, in Drosophila indicates that the molecular compositions of sSJs and pSJs differ. A deficiency screen based on immunolocalization of Mesh identified a tetraspanin family protein, Tsp2A, as a newly discovered protein involved in sSJ formation in Drosophila. Tsp2A specifically localizes at sSJs in the midgut and Malpighian tubules. CompromisedTsp2AexpressioncausedbyRNAior the CRISPR/Cas9 system was associated with defects in the ultrastructure of sSJs, changed localization of other sSJ proteins, and impaired barrier function of themidgut. Inmost Tsp2Amutant cells, Mesh failed to localize to sSJs and was distributed through the cytoplasm. Tsp2A forms a complex with Mesh and Ssk and these proteins are mutually interdependent for their localization. These observations suggest that Tsp2A cooperates with Mesh and Ssk to organize sSJs.