Department of Molecular and Human Genetics, Institute of Science, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India.
J Cell Sci. 2022 Sep 1;135(17). doi: 10.1242/jcs.259658. Epub 2022 Sep 7.
Deltex (Dx) is a context-dependent regulator of Notch signaling that can act in a non-canonical fashion by facilitating the endocytosis of the Notch receptor. In an RNAi-based modifier screen of kinases and phosphatases, we identified Thickveins (Tkv), the receptor of Decapentaplegic (Dpp), as one of the interactors of Dx. Dpp, a Drosophila homolog of TGF-β and bone morphogenetic proteins, acts as a morphogen to specify cell fate along the anterior-posterior axis of the wing. Tight regulation of Dpp signaling is thus indispensable for its proper functioning. Here, we present Dx as a novel modulator of Dpp signaling. We show evidence for the very first time that dx genetically interacts with dpp and its pathway components. Immunocytochemical analysis revealed that Dx colocalizes with Dpp and its receptor Tkv in Drosophila third-instar larval tissues. Furthermore, Dx was also seen to modulate the expression of dpp and its target genes, and we attribute this modulation to the involvement of Dx in the endocytosis and trafficking of Dpp. This study thus presents a whole new avenue of Dpp signaling regulation via the cytoplasmic protein Dx. This article has an associated First Person interview with the first author of the paper.
德尔泰克斯(Dx)是 Notch 信号的一种上下文相关的调节剂,它可以通过促进 Notch 受体的内吞作用以非经典的方式发挥作用。在基于 RNAi 的激酶和磷酸酶调节剂筛选中,我们鉴定了 Thickveins(Tkv),即 Decapentaplegic(Dpp)的受体,是 Dx 的相互作用蛋白之一。Dpp 是果蝇中 TGF-β和骨形态发生蛋白的同源物,作为一种形态发生素沿翅膀的前后轴指定细胞命运。因此,Dpp 信号的紧密调节对于其正常功能是必不可少的。在这里,我们提出 Dx 是 Dpp 信号的一种新型调节剂。我们首次提供证据表明 dx 与 dpp 及其途径成分在遗传上相互作用。免疫细胞化学分析显示,Dx 在果蝇三龄幼虫组织中与 Dpp 和其受体 Tkv 共定位。此外,还观察到 Dx 调节 dpp 及其靶基因的表达,我们将这种调节归因于 Dx 参与 Dpp 的内吞作用和运输。因此,这项研究通过细胞质蛋白 Dx 为 Dpp 信号转导提供了一个全新的调节途径。本文有一篇对该论文第一作者的第一人称采访。