The atypical mammalian ligand Delta-like homologue 1 (Dlk1) can regulate Notch signalling in Drosophila.
The atypical mammalian ligand Delta-like homologue 1 (Dlk1) can regulate Notch signalling in Drosophila.
复制标题
DOI：
10.1186/1471-213x-8-11
复制
发表时间：
2008-01-31
影响因子：
--
通讯作者：
Ferguson-Smith, Anne C.
中科院分区：
文献类型：
--
作者：
Bray, Sarah J.;Takada, Shuji;Harrison, Emma;Shen, Shing-Chuan;Ferguson-Smith, Anne C.
哺乳动物Delta-like 1（Dlk-1）蛋白与Notch配体具有同源性，但缺乏关键的受体结合结构域。因此，尚不清楚它是否能够在体内与Notch相互作用。与哺乳动物不同，果蝇有一个单一的Notch受体，允许简单的哺乳动物Dlk 1功能的体内测定。在这里，我们表明，膜结合DLK 1可以调节Notch，导致Notch本身的细胞分布改变，并抑制Notch靶基因的表达。所得的成体表型指示Notch功能降低，并且通过Notch突变增强，证实DLK 1作用是拮抗性的。此外，表达另一种Dlk 1亚型的细胞表现出细胞大小的改变，这些功能以前不属于Notch，这表明DLK 1也可能通过另一种靶点起作用。我们的研究结果表明，DLK 1可以调节Notch受体，尽管它的非典型结构。
Mammalian Delta-like 1 (Dlk-1) protein shares homology with Notch ligands but lacks a critical receptor-binding domain. Thus it is unclear whether it is able to interact with Notch in vivo. Unlike mammals, Drosophila have a single Notch receptor allowing a simple in vivo assay for mammalian Dlk1 function. Here we show that membrane-bound DLK1 can regulate Notch leading to altered cellular distribution of Notch itself and inhibiting expression of Notch target genes. The resulting adult phenotypes are indicative of reduced Notch function and are enhanced by Notch mutations, confirming that DLK1 action is antagonistic. In addition, cells expressing an alternative Dlk1 isoform exhibit alterations in cell size, functions previously not attributed to Notch suggesting that DLK1 might also act via an alternative target. Our results demonstrate that DLK1 can regulate the Notch receptor despite its atypical structure.