Yan Dong, Wu Yihui, Feng Ying, Lin Sheng-Cai, Lin Xinhua
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Dev Cell. 2009 Oct;17(4):470-81. doi: 10.1016/j.devcel.2009.09.001.
Dally-like (Dlp) is a glypican-type heparan sulfate proteoglycan (HSPG), containing a protein core and attached glycosaminoglycan (GAG) chains. In Drosophila wing discs, Dlp represses short-range Wingless (Wg) signaling, but activates long-range Wg signaling. Here, we show that Dlp core protein has similar biphasic activity as wild-type Dlp. Dlp core protein can interact with Wg; the GAG chains enhance this interaction. Importantly, we find that Dlp exhibits a biphasic response, regardless of whether its glycosylphosphatidylinositol linkage to the membrane can be cleaved. Rather, the transition from signaling activator to repressor is determined by the relative expression levels of Dlp and the Wg receptor, Frizzled (Fz) 2. Based on these data, we propose that the principal function of Dlp is to retain Wg on the cell surface. As such, it can either compete with the receptor or provide ligands to the receptor, depending on the ratios of Wg, Fz2, and Dlp.
类Dally（Dlp）是一种磷脂酰肌醇蛋白聚糖型硫酸乙酰肝素蛋白聚糖（HSPG），含有一个蛋白核心和连接的糖胺聚糖（GAG）链。在果蝇翅盘中，Dlp抑制短程无翅（Wg）信号传导，但激活长程Wg信号传导。在这里，我们表明Dlp核心蛋白具有与野生型Dlp相似的双相活性。Dlp核心蛋白可以与Wg相互作用；GAG链增强了这种相互作用。重要的是，我们发现无论Dlp与膜的糖基磷脂酰肌醇连接是否可被切割，Dlp都表现出双相反应。相反，从信号激活剂到抑制剂的转变取决于Dlp和Wg受体卷曲蛋白（Fz）2的相对表达水平。基于这些数据，我们提出Dlp的主要功能是将Wg保留在细胞表面。因此，根据Wg、Fz2和Dlp的比例，它可以与受体竞争或为受体提供配体。
