Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3200, USA.
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3200, USA
Development. 2014 Jul;141(14):2796-802. doi: 10.1242/dev.105403.
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.
画线（Scrib）模块蛋白是细胞极性的主要调节剂，但它们如何影响膜运输尚不清楚。内吞作用也是通过其作用来调节极性的关键因素，但其作用仍不清楚。在这里，我们将 Scrib 与内吞作用的特定途径联系起来。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似的表型，但 Scrib 模块突变体显示完整的内化和内体溶酶体运输。然而，观察到逆行途径货物的运输缺陷，并且逆行成分与 Scrib 模块表现出强烈的遗传相互作用。Scrib 模块对于逆行蛋白正确定位到内体是必需的，并通过依赖和不依赖 aPKC 的机制促进适当的货物分选到逆行途径中。我们提出，Scrib 模块通过影响 Crumbs 和其他依赖逆行蛋白的货物的内吞作用途径来调节上皮极性。
