Ykt6-dependent endosomal recycling is required for Wnt secretion in the Drosophila wing epithelium
Ykt6-dependent endosomal recycling is required for Wnt secretion in the Drosophila wing epithelium
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DOI：
10.1242/dev.185421
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发表时间：
2020-08-01
期刊：
影响因子：
4.6
通讯作者：
Gross, Julia Christina
中科院分区：
文献类型：
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作者：
Linnemannstoens, Karen;Witte, Leonie;Gross, Julia Christina
形态发生素是组织发育的重要信号分子，其分泌需要严格调控。在果蝇的翼成虫盘中，形态发生素 Wnt/Wingless 由分泌细胞在顶部呈递，并在最终的远程分泌之前重新内化。为什么 Wnt 分子经历这些运输步骤以及内体区室内调节控制的性质仍不清楚。在这里，我们研究了多功能 v-SNARE Ykt6 如何在内体水平上对 Wnt 进行排序。利用体内遗传学、邻近依赖性蛋白质组学和体外生化分析，我们表明大多数 Ykt6 存在于细胞质中，但可以被募集到脱酸区室并通过 Rab4 阳性回收内体将 Wnt 回收到质膜。因此，我们提出了一种分子机制，通过该分子机制，生产细胞通过 Ykt6 整合并利用内吞作用和回收来协调细胞外 Wnt 水平。
Morphogens are important signalling molecules for tissue development and their secretion requires tight regulation. In the wing imaginal disc of flies, the morphogen Wnt/Wingless is apically presented by the secreting cell and re-internalized before final long-range secretion. Why Wnt molecules undergo these trafficking steps and the nature of the regulatory control within the endosomal compartment remain unclear. Here, we have investigated how Wnts are sorted at the level of endosomes by the versatile v-SNARE Ykt6. Using in vivo genetics, proximity-dependent proteomics and in vitro biochemical analyses, we show that most Ykt6 is present in the cytosol, but can be recruited to de-acidified compartments and recycle Wnts to the plasma membrane via Rab4-positive recycling endosomes. Thus, we propose a molecular mechanism by which producing cells integrate and leverage endocytosis and recycling via Ykt6 to coordinate extracellular Wnt levels.