Drosophila Dpp morphogen movement is independent of dynamin-mediated endocytosis but regulated by the glypican members of heparan sulfate proteoglycans
Drosophila Dpp morphogen movement is independent of dynamin-mediated endocytosis but regulated by the glypican members of heparan sulfate proteoglycans
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DOI：
10.1016/j.cell.2004.09.031
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发表时间：
2004-10-15
期刊：
影响因子：
64.5
通讯作者：
Lin, XH
中科院分区：
文献类型：
--
作者：
Belenkaya, TY;Han, C;Lin, XH
果蝇转化生长因子β（TGF-β）同源物Decapentaplegic（Dpp）作为一种形态发生剂，形成一个长范围的浓度梯度，以指导翅膀的前后图案。已经提出了由发动蛋白介导的内吞作用和细胞外扩散引发的平面转胞吞作用用于Dpp跨细胞移动。在这项工作中，我们发现Dpp主要是胞外的，其胞外梯度与其活性梯度相吻合。我们表明，内吞的动力蛋白突变shibire的封锁不阻止DPP运动，而是抑制DPP信号转导，这表明内吞是不是必不可少的DPP运动，但参与DPP信号。此外，我们发现Dpp不能跨细胞突变体daily和daily-like（dly），两个果蝇磷脂酰肌醇蛋白聚糖硫酸肝素蛋白聚糖（HSPG）的成员。我们的研究结果支持一个模型，其中DPP移动沿着细胞表面的限制性细胞外扩散涉及磷脂酰肌醇蛋白聚糖的日常和Dly。
The Drosophila transforming growth factor beta(TGF-beta) homolog Decapentaplegic (Dpp) acts as a morphogen that forms a long-range concentration gradient to direct the anteroposterior patterning of the wing. Both planar transcytosis initiated by Dynamin-mediated endocytosis and extracellular diffusion have been proposed for Dpp movement across cells. In this work, we found that Dpp is mainly extracellular, and its extracellular gradient coincides with its activity gradient. We demonstrate that a blockage of endocytosis by the dynamin mutant shibire does not block Dpp movement but rather inhibits Dpp signal transduction, suggesting that endocytosis is not essential for Dpp movement but is involved in Dpp signaling. Furthermore, we show that Dpp fails to move across cells mutant for daily and daily-like (dly), two Drosophila glypican members of heparin sulfate proteoglycan (HSPG). Our results support a model in which Dpp moves along the cell surface by restricted extracellular diffusion involving the glypicans Daily and Dly.