Formation of a Bazooka-Stardust complex is essential for plasma membrane polarity in epithelia.
Formation of a Bazooka-Stardust complex is essential for plasma membrane polarity in epithelia.
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DOI：
10.1083/jcb.201006029
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发表时间：
2010-09-06
期刊：
影响因子：
--
通讯作者：
Wodarz A
中科院分区：
文献类型：
--
作者：
Krahn MP;Bückers J;Kastrup L;Wodarz A
Crumbs-Stardust极性复合体的招募依赖于Bazooka和Stardust PDZ结构域之间的相互作用，并受PKC介导的磷酸化调节。果蝇黑腹果蝇上皮细胞顶端-基底端的极性取决于几个进化上保守的蛋白质，它们被分配到两个不同的蛋白质复合体：Bazooka(Baz)-PAR-6(分割缺陷6)-非典型蛋白激酶C(APKC)复合体和Crumbs(CRB)-Stardust(SDT)复合体。这些蛋白质在功能层次中工作，其中BAZ是所有其他蛋白质正确的亚细胞定位所必需的。我们研究了这些蛋白质是如何相互作用的，以及这种相互作用是如何受到调控的。我们发现，Baz通过SDT的突触后密度95/Discs Large/Zonula occludens 1(PDZ)结构域与BaZ中包含一个pPKC磷酸化位点的区域直接相互作用，将SDT招募到质膜上。Baz的磷酸化导致Baz-SDT复合体的解离。过度表达一个非磷酸化版本的BaZ可以阻止SDT从BaZ中解离，导致与CRB和SDT突变非常相似的表型。我们的发现为Baz-PAR-3和CRB复合体之间的磷酸化依赖的相互作用提供了一个分子机制。
Recruitment of the Crumbs–Stardust polarity complex depends on interactions between Bazooka and the Stardust PDZ domain and is regulated by aPKC-mediated phosphorylation. Apical–basal polarity in Drosophila melanogaster epithelia depends on several evolutionarily conserved proteins that have been assigned to two distinct protein complexes: the Bazooka (Baz)–PAR-6 (partitioning defective 6)–atypical protein kinase C (aPKC) complex and the Crumbs (Crb)–Stardust (Sdt) complex. These proteins operate in a functional hierarchy, in which Baz is required for the proper subcellular localization of all other proteins. We investigated how these proteins interact and how this interaction is regulated. We show that Baz recruits Sdt to the plasma membrane by direct interaction between the Postsynaptic density 95/Discs large/Zonula occludens 1 (PDZ) domain of Sdt and a region of Baz that contains a phosphorylation site for aPKC. Phosphorylation of Baz causes the dissociation of the Baz–Sdt complex. Overexpression of a nonphosphorylatable version of Baz blocks the dissociation of Sdt from Baz, causing phenotypes very similar to those of crb and sdt mutations. Our findings provide a molecular mechanism for the phosphorylation-dependent interaction between the Baz–PAR-3 and Crb complexes during the establishment of epithelial polarity.
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