Cellular trafficking of the glypican dally-like is required for full-strength Hedgehog signaling and Wingless transcytosis
Cellular trafficking of the glypican dally-like is required for full-strength Hedgehog signaling and Wingless transcytosis
复制标题
细胞转运糖蛋白达利样是全强度刺猬信号传递和无翼鸟转细胞的必要条件
DOI：
10.1016/j.devcel.2008.03.001
复制
发表时间：
2008-05-01
影响因子：
11.8
通讯作者：
Therond, Pascal P.
中科院分区：
文献类型：
--
作者：
Gallet, Armel;Staccini-Lavenant, Laurence;Therond, Pascal P.
刺猬（Hh）和无翼（Wg）形态因子在果蝇翅膀想象盘中以浓度依赖的方式指定细胞命运。蛋白聚糖是细胞外基质的组成部分，参与Hh和Wg的稳定性、扩散和接受。在这项研究中，我们证明糖基磷脂酰肌醇（GPI）锚定在glypican Dally-like （Dip）的根尖内化和随后靶向上皮基底外侧室是必需的。Hh受体细胞顶表面的浸渍内吞作用可催化与其受体复合物（Ptc）结合的Hh内化。Dip与Hh/Ptc复合物的共内在化是动力蛋白依赖的，并且是全方位Hh信号传导所必需的。我们也证明了Wg是在椎间盘上皮的顶端分泌的，并且Dip的顶端基底运输允许Wg经细胞作用有利于Wg沿基底外侧腔室扩散。因此，Dip内吞作用是Hh和Wg形态因子作用的共同调节机制。
Hedgehog (Hh) and Wingless (Wg) morphogens specify cell fate in a concentration-dependent manner in the Drosophila wing imaginal disc. Proteoglycans, components of the extracellular matrix, are involved in Hh and Wg stability, spreading, and reception. In this study, we demonstrate that the glycosyl-phosphatidyl-inositol (GPI) anchor of the glypican Dally-like (Dip) is required for its apical internalization and its subsequent targeting to the basolateral compartment of the epithelium. Dip endocytosis from the apical surface of Hh-receiving cells catalyzes the internalization of Hh bound to its receptor Patched (Ptc). The cointernalization of Dip with the Hh/Ptc complex is dynamin dependent and necessary for full-strength Hh signaling. We also demonstrate that Wg is secreted apically in the disc epithelium and that apicobasal trafficking of Dip allows Wg transcytosis to favor Wg spreading along the basolateral compartment. Thus, Dip endocytosis is a common regulatory mechanism of both Hh and Wg morphogen action.