Dlg5 maintains apical polarity by promoting membrane localization of Crumbs during Drosophila oogenesis
Dlg5 maintains apical polarity by promoting membrane localization of Crumbs during Drosophila oogenesis
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DOI：
10.1038/srep26553
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发表时间：
2016-05
影响因子：
4.6
通讯作者：
Jun Luo;Heng Wang;Di Kang;Xuan Guo;P. Wan;Dou Wang;Jiong Chen
中科院分区：
文献类型：
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作者：
Jun Luo;Heng Wang;Di Kang;Xuan Guo;P. Wan;Dou Wang;Jiong Chen
顶基极性在上皮组织的功能中起着关键作用。然而，上皮极性建立和维持的机制仍有待充分阐明。在这里，我们表明，膜相关鸟苷酸激酶（MAGUK）家族蛋白Dlg 5是必需的维持顶端极性的卵泡上皮细胞在果蝇卵子发生。Dlg 5定位于早期卵腔卵泡上皮的顶膜和粘附连接处（AJ）。具体而言，我们证明Dlg 5的主要功能是促进Crumbs的顶端膜定位，因为Crumbs的过表达而不是其他主要的顶端或AJ组分可以挽救由Dlg 5的缺失导致的上皮极性缺陷。此外，我们对Dlg 5进行了结构-功能分析，发现C-末端PDZ 3和PDZ 4结构域是Dlg 5所有功能以及定位于顶膜的能力所必需的。N-末端卷曲螺旋基序可以单独靶向顶膜，而中心接头区域可以靶向AJ。最后，PDZ 4-SH 3-GUK的MAGUK核心结构域可以单独靶向顶膜、AJ膜和基底外侧膜。
Apical-basal polarity plays critical roles in the functions of epithelial tissues. However, the mechanisms of epithelial polarity establishment and maintenance remain to be fully elucidated. Here we show that the membrane-associated guanylate kinase (MAGUK) family protein Dlg5 is required for the maintenance of apical polarity of follicle epithelium during Drosophila oogenesis. Dlg5 localizes at the apical membrane and adherens junction (AJ) of follicle epithelium in early stage egg chambers. Specifically, we demonstrate that the major function of Dlg5 is to promote apical membrane localization of Crumbs, since overexpression of Crumbs but not other major apical or AJ components could rescue epithelial polarity defects resulted from loss of Dlg5. Furthermore, we performed a structure-function analysis of Dlg5 and found that the C-terminal PDZ3 and PDZ4 domains are required for all Dlg5’s functions as well as its ability to localize to apical membrane. The N-terminal coiled-coil motif could be individually targeted to the apical membrane, while the central linker region could be targeted to AJ. Lastly, the MAGUK core domains of PDZ4-SH3-GUK could be individually targeted to apical, AJ and basolateral membranes.