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顶端决定因子非典型蛋白激酶C(aPKC)和盘状蛋白(dPatj)在果蝇眼睛中调节依赖卷曲蛋白(Frizzled)的平面细胞极性。

The apical determinants aPKC and dPatj regulate Frizzled-dependent planar cell polarity in the Drosophila eye.

作者信息

Djiane Alexandre, Yogev Shaul, Mlodzik Marek

机构信息

Brookdale Department of Molecular, Cell and Developmental Biology, Mount Sinai School of Medicine, New York, New York 10029.

Brookdale Department of Molecular, Cell and Developmental Biology, Mount Sinai School of Medicine, New York, New York 10029.

出版信息

Cell. 2005 May 20;121(4):621-631. doi: 10.1016/j.cell.2005.03.014.

Abstract

Planar cell polarity (PCP) is a common feature of many vertebrate and invertebrate epithelia and is perpendicular to their apical/basal (A/B) polarity axis. While apical localization of PCP determinants such as Frizzled (Fz1) is critical for their function, the link between A/B polarity and PCP is poorly understood. Here, we describe a direct molecular link between A/B determinants and Fz1-mediated PCP establishment in the Drosophila eye. We demonstrate that dPatj binds the cytoplasmic tail of Fz1 and propose that it recruits aPKC, which in turn phosphorylates and inhibits Fz1. Accordingly, components of the aPKC complex and dPatj produce PCP defects in the eye. We also show that during PCP signaling, aPKC and dPatj are downregulated, while Bazooka is upregulated, suggesting an antagonistic effect of Bazooka on dPatj/aPKC. We propose a model whereby the dPatj/aPKC complex regulates PCP by inhibiting Fz1 in cells where it should not be active.

摘要

平面细胞极性(PCP)是许多脊椎动物和无脊椎动物上皮细胞的共同特征,且与它们的顶/基(A/B)极性轴垂直。虽然PCP决定因子(如卷曲蛋白1,Fz1)的顶端定位对其功能至关重要,但A/B极性与PCP之间的联系却鲜为人知。在此,我们描述了果蝇眼中A/B决定因子与Fz1介导的PCP建立之间的直接分子联系。我们证明dPatj与Fz1的细胞质尾部结合,并提出它招募非典型蛋白激酶C(aPKC),而aPKC反过来磷酸化并抑制Fz1。相应地,aPKC复合物和dPatj的成分在眼中产生PCP缺陷。我们还表明,在PCP信号传导过程中,aPKC和dPatj被下调,而巴祖卡蛋白(Bazooka)被上调,这表明巴祖卡蛋白对dPatj/aPKC具有拮抗作用。我们提出了一个模型,即dPatj/aPKC复合物通过在不应活跃的细胞中抑制Fz1来调节PCP。

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