The Scribble module regulates retromer-dependent endocytic trafficking during epithelial polarization
The Scribble module regulates retromer-dependent endocytic trafficking during epithelial polarization
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DOI：
10.1242/dev.105403
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发表时间：
2014-07-01
期刊：
影响因子：
4.6
通讯作者：
Bilder, David
中科院分区：
文献类型：
--
作者：
de Vreede, Geert;Schoenfeld, Joshua D.;Bilder, David
Scribble （Scrib）模块蛋白是细胞极性的主要调节因子，但它们如何影响膜交通尚不清楚。内吞作用也是极性的关键调节因子，其作用尚不清楚。这里我们将Scrib与内吞贩运系统的一个特定分支联系起来。阻断ap -2依赖性内吞作用的果蝇突变体与Scrib模块突变体具有许多相同的表型，但Scrib模块突变体表现出完整的内化和内溶酶体运输。然而，逆转录酶途径货物的缺陷运输被发现，逆转录酶组分与Scrib模块表现出强烈的遗传相互作用。Scrib模块是逆转录酶正确定位到核内体所必需的，并通过apkc依赖性和非依赖性机制促进逆转录酶途径中适当的货物分类。我们提出Scrib模块通过影响碎屑和其他依赖后转录物的内吞行程来调节上皮极性。
Scribble (Scrib) module proteins are major regulators of cell polarity, but how they influence membrane traffic is not known. Endocytosis is also a key regulator of polarity through roles that remain unclear. Here we link Scrib to a specific arm of the endocytic trafficking system. Drosophila mutants that block AP-2-dependent endocytosis share many phenotypes with Scrib module mutants, but Scrib module mutants show intact internalization and endolysosomal transport. However, defective traffic of retromer pathway cargo is seen, and retromer components show strong genetic interactions with the Scrib module. The Scrib module is required for proper retromer localization to endosomes and promotes appropriate cargo sorting into the retromer pathway via both aPKC-dependent and -independent mechanisms. We propose that the Scrib module regulates epithelial polarity by influencing endocytic itineraries of Crumbs and other retromer-dependent cargo.