The Drosophila ZO-1 protein Polychaetoid suppresses Deltex-regulated Notch activity to modulate germline stem cell niche formation.
The Drosophila ZO-1 protein Polychaetoid suppresses Deltex-regulated Notch activity to modulate germline stem cell niche formation.
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DOI：
10.1098/rsob.160322
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发表时间：
2017-04
期刊：
影响因子：
5.8
通讯作者：
Baron M
中科院分区：
文献类型：
--
作者：
Shimizu H;Wilkin MB;Woodcock SA;Bonfini A;Hung Y;Mazaleyrat S;Baron M
发育信号蛋白Notch可以在细胞表面的配体相互作用后被蛋白水解激活，或者可以在Deltex（Dx）诱导的Notch内吞作用和运输到溶酶体膜后独立于其配体被激活。不同的Notch池指向这些替代结果的手段仍然知之甚少。我们发现，果蝇ZO-1蛋白多毛类（Pyd）抑制特异性Dx诱导的Notch激活形式在体内和细胞培养试验。在体内，我们证实了生理相关性和方向的Pyd/Dx的相互作用，显示扩大卵巢干细胞的小生境表型的pyd突变体需要存在的功能Dx和其他组件，是特定的Dx诱导的Notch激活机制。在S2细胞中，我们发现Pyd可以与Dx和Notch在细胞表面形成复合物，并减少Dx诱导的Notch内吞。与ZO-1家族蛋白的其他已知活性类似，发现Pyd对Dx诱导的内吞作用和信号传导的作用是细胞密度依赖性的。因此，总之，我们的研究结果表明，外部线索可以通过Pyd调节Dx诱导的Notch贩运来调整Notch信号传导的替代手段。
The developmental signalling protein Notch can be proteolytically activated following ligand-interaction at the cell surface, or can be activated independently of its ligands, following Deltex (Dx)-induced Notch endocytosis and trafficking to the lysosomal membrane. The means by which different pools of Notch are directed towards these alternative outcomes remains poorly understood. We found that the Drosophila ZO-1 protein Polychaetoid (Pyd) suppresses specifically the Dx-induced form of Notch activation both in vivo and in cell culture assays. In vivo we confirmed the physiological relevance and direction of the Pyd/Dx interaction by showing that the expanded ovary stem cell niche phenotypes of pyd mutants require the presence of functional Dx and other components that are specific to the Dx-induced Notch activation mechanism. In S2 cells we found that Pyd can form a complex with Dx and Notch at the cell surface and reduce Dx-induced Notch endocytosis. Similar to other known activities of ZO-1 family proteins, the action of Pyd on Dx-induced endocytosis and signalling was found to be cell density dependent. Thus, together, our results suggest an alternative means by which external cues can tune Notch signalling through Pyd regulation of Dx-induced Notch trafficking.