Cholesterol modification of hedgehog is required for trafficking and movement, revealing an asymmetric cellular response to hedgehog
Cholesterol modification of hedgehog is required for trafficking and movement, revealing an asymmetric cellular response to hedgehog
复制标题
DOI：
10.1016/s1534-5807(03)00031-5
复制
发表时间：
2003-02-01
影响因子：
11.8
通讯作者：
Therond, PP
中科院分区：
文献类型：
--
作者：
Gallet, A;Rodriguez, R;Therond, PP
Hedgehog家族成员是参与多种模式机制的分泌蛋白。不同的翻译后修饰已被证明可以调节 Hedgehog 的生物活性。我们研究了这些修饰在调节果蝇胚胎上皮细胞中 Hedgehog 的亚细胞定位中的作用。我们证明，Hedgehog 的胆固醇修饰负责其在大点状结构中的组装以及通过含有甾醇感应结构域的 Dispatched 蛋白的活性进行顶端分选。我们进一步表明，这些特殊结构在细胞场中的运动取决于硫酸乙酰肝素聚合酶 Tout-Velu 合成的蛋白聚糖的活性。最后，我们表明，Hedgehog 大点状结构仅对于跨节段边界的 Hedgehog 靶基因子集是必需的，这表明来自不同膜区室的 Hedgehog 的呈现是上皮细胞中 Hedgehog 功能多样性的原因。
Hedgehog family members are secreted proteins involved in numerous patterning mechanisms. Different posttranslational modifications have been shown to modulate Hedgehog biological activity. We investigated the role of these modifications in regulating subcellular localization of Hedgehog in the Drosophila embryonic epithelium. We demonstrate that cholesterol modification of Hedgehog is responsible for its assembly in large punctate structures and apical sorting through the activity of the sterol-sensing domain-containing Dispatched protein. We further show that movement of these specialized structures through the cellular field is contingent upon the activity of proteoglycans synthesized by the heparan sulfate polymerase Tout-Velu. Finally, we show that the Hedgehog large punctate structures are necessary only for a subset of Hedgehog target genes across the parasegmental boundary, suggesting that presentation of Hedgehog from different membrane compartments is responsible for Hedgehog functional diversity in epithelial cells.