Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Stem Cell Reports. 2020 May 12;14(5):828-844. doi: 10.1016/j.stemcr.2020.03.021. Epub 2020 Apr 23.
Tight junctions in mammals and septate junctions in insects are essential for epithelial integrity. We show here that, in the Drosophila intestine, smooth septate junction proteins provide barrier and signaling functions. During an RNAi screen for genes that regulate adult midgut tissue growth, we found that loss of two smooth septate junction components, Snakeskin and Mesh, caused a hyperproliferation phenotype. By examining epitope-tagged endogenous Snakeskin and Mesh, we demonstrate that the two proteins are present in the cytoplasm of differentiating enteroblasts and in cytoplasm and septate junctions of mature enterocytes. In both enteroblasts and enterocytes, loss of Snakeskin and Mesh causes Yorkie-dependent expression of the JAK-STAT pathway ligand Upd3, which in turn promotes proliferation of intestinal stem cells. Snakeskin and Mesh form a complex with each other, with other septate junction proteins and with Yorkie. Therefore, the Snakeskin-Mesh complex has both barrier and signaling function to maintain stem cell-mediated tissue homeostasis.
哺乳动物中的紧密连接和昆虫中的隔膜连接对于上皮组织的完整性至关重要。我们在这里表明，在果蝇的肠道中，光滑的隔膜连接蛋白具有屏障和信号功能。在一个针对调节成年中肠组织生长的基因的 RNAi 筛选中，我们发现两种光滑隔膜连接成分 SnakeSkin 和 Mesh 的缺失导致了过度增殖表型。通过检查内源性标记的 SnakeSkin 和 Mesh，我们证明这两种蛋白质存在于分化中的肠母细胞的细胞质中和成熟的肠细胞的细胞质和隔膜连接中。在肠母细胞和肠细胞中，SnakeSkin 和 Mesh 的缺失导致依赖于 Yorkie 的 JAK-STAT 通路配体 Upd3 的表达，这反过来又促进了肠道干细胞的增殖。SnakeSkin 和 Mesh 彼此之间形成复合物，与其他隔膜连接蛋白和 Yorkie 形成复合物。因此，SnakeSkin-Mesh 复合物具有屏障和信号功能，以维持干细胞介导的组织稳态。
