Chang Yung-Heng, Sun Yi Henry
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China; Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan, Republic of China.
PLoS One. 2014 Oct 31;9(10):e111573. doi: 10.1371/journal.pone.0111573. eCollection 2014.
Morphogens are signaling molecules that regulate growth and patterning during development by forming a gradient and activating different target genes at different concentrations. The extracellular distribution of morphogens is tightly regulated, with the Drosophila morphogen Wingless (Wg) relying on Dally-like (Dlp) and transcytosis for its distribution. However, in the absence of Dlp or endocytic activity, Wg can still move across cells along the apical (Ap) surface. We identified a novel secreted heparan sulfate proteoglycan (HSPG) that binds to Wg and promotes its extracellular distribution by increasing Wg mobility, which was thus named Carrier of Wg (Cow). Cow promotes the Ap transport of Wg, independent of Dlp and endocytosis, and this function addresses a previous gap in the understanding of Wg movement. This is the first example of a diffusible HSPG acting as a carrier to promote the extracellular movement of a morphogen.
形态发生素是一类信号分子,在发育过程中通过形成浓度梯度并在不同浓度下激活不同的靶基因来调节生长和模式形成。形态发生素的细胞外分布受到严格调控,果蝇形态发生素无翅(Wg)依靠类Dally(Dlp)蛋白和转胞吞作用进行分布。然而,在缺乏Dlp或内吞活性的情况下,Wg仍可沿顶端(Ap)表面跨细胞移动。我们鉴定出一种新型的分泌型硫酸乙酰肝素蛋白聚糖(HSPG),它与Wg结合并通过增加Wg的移动性来促进其细胞外分布,因此将其命名为Wg载体(Cow)。Cow促进Wg的Ap运输,不依赖于Dlp和内吞作用,这一功能填补了之前对Wg移动理解上的空白。这是可扩散的HSPG作为载体促进形态发生素细胞外移动的首个例子。