PDF(Pubmed)
Abstract：
Dpp/BMP acts as a morphogen to provide positional information in the Drosophila wing disc. Key cell-surface molecules to control Dpp morphogen gradient formation and signaling are heparan sulfate proteoglycans (HSPGs). In the wing disc, two HSPGs, the glypicans Division abnormally delayed (Dally) and Dally-like (Dlp) have been suggested to act redundantly to control these processes through direct interaction of their heparan sulfate (HS) chains with Dpp. Based on this assumption, a number of models on how glypicans control Dpp gradient formation and signaling have been proposed, including facilitating or hindering Dpp spreading, stabilizing Dpp on the cell surface, or recycling Dpp. However, how distinct HSPGs act remains largely unknown. Here, we generate genome-engineering platforms for the two glypicans and find that only Dally is critical for Dpp gradient formation and signaling through interaction of its core protein with Dpp. We also find that this interaction is not sufficient and that the HS chains of Dally are essential for these functions largely without interacting with Dpp. We provide evidence that the HS chains of Dally are not essential for spreading or recycling of Dpp but for stabilizing Dpp on the cell surface by antagonizing receptor-mediated Dpp internalization. These results provide new insights into how distinct HSPGs control morphogen gradient formation and signaling during development.
摘要：
Dpp/BMP充当形态素以提供果蝇翼盘中的位置信息。控制Dpp形态发生原梯度形成和信号传导的关键细胞表面分子是硫酸乙酰肝素蛋白聚糖(HSPG)。在机翼圆盘中，两个HSPG，已经建议磷脂酰肌醇分裂异常延迟（Dally）和Dally样（Dlp）通过其硫酸乙酰肝素（HS）链与Dpp的直接相互作用来冗余地控制这些过程。基于这个假设,已经提出了许多关于字形如何控制Dpp梯度形成和信号传导的模型，包括促进或阻碍民进党的传播，在细胞表面稳定Dpp，或回收Dpp。然而,HSPGs的作用方式在很大程度上还不清楚。这里,我们为这两种配体生成了基因组工程平台，发现只有Dally通过其核心蛋白与Dpp的相互作用对Dpp梯度形成和信号传导至关重要。我们还发现，这种相互作用是不够的，并且Dally的HS链对于这些功能至关重要，而无需与Dpp相互作用。我们提供的证据表明，Dally的HS链对于Dpp的传播或再循环不是必需的，而是通过拮抗受体介导的Dpp内化来稳定细胞表面上的Dpp。这些结果为不同的HSPG如何在发育过程中控制形态发生原梯度形成和信号传导提供了新的见解。
