Dpp gradient formation by dynamin-dependent endocytosis:: receptor trafficking and the diffusion model
Dpp gradient formation by dynamin-dependent endocytosis:: receptor trafficking and the diffusion model
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DOI：
10.1242/dev.01335
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发表时间：
2004-10-01
期刊：
影响因子：
4.6
通讯作者：
González-Gaitán, M
中科院分区：
文献类型：
--
作者：
Kruse, K;Pantazis, P;González-Gaitán, M
发育中的细胞通过读取形态因子的分级分布来获取位置信息。在果蝇中，Dpp形态原通过在发育的翅膀中从一个受限的来源扩散形成一个长期的浓度梯度。人们一直认为Dpp是通过细胞外扩散传播的。在这种假设下，内吞作用在梯度形成中的主要作用是下调细胞表面的受体。这些表面受体与配体结合，从而干扰其远距离运动。最近的实验表明，Dpp的扩散是由靶组织中动力蛋白依赖的内吞作用介导的，这表明细胞外扩散不能单独解释Dpp的扩散。在这里，我们对基于细胞外扩散的形态原扩散模型进行了理论研究，该模型考虑了受体结合和运输。我们将该模型中获得的配体和表面受体的轮廓与实验数据进行了比较。为此，我们直接监测了具有特异性抗体的表面受体和细胞外Dpp池。我们的结论是，目前考虑纯细胞外扩散的模型不能解释在Dpp远程运动中观察到的内吞作用。
Developing cells acquire positional information by reading the graded distribution of morphogens. In Drosophila, the Dpp morphogen forms a long-range concentration gradient by spreading from a restricted source in the developing wing. It has been assumed that Dpp spreads by extracellular diffusion. Under this assumption, the main role of endocytosis in gradient formation is to downregulate receptors at the cell surface. These surface receptors bind to the ligand and thereby interfere with its long-range movement. Recent experiments indicate that Dpp spreading is mediated by Dynamin-dependent endocytosis in the target tissue, suggesting that extracellular diffusion alone cannot account for Dpp dispersal. Here, we perform a theoretical study of a model for morphogen spreading based on extracellular diffusion, which takes into account receptor binding and trafficking. We compare profiles of ligand and surface receptors obtained in this model with experimental data. To this end, we monitored directly the pool of surface receptors and extracellular Dpp with specific antibodies. We conclude that current models considering pure extracellular diffusion cannot explain the observed role of endocytosis during Dpp long-range movement.