Jenny Andreas, Reynolds-Kenneally Jessica, Das Gishnu, Burnett Micheal, Mlodzik Marek
Mount Sinai School of Medicine, Brookdale Department of Molecular, Cellular and Developmental Biology, 1 Gustave L. Levy Place, New York, NY 10029, USA.
Nat Cell Biol. 2005 Jul;7(7):691-7. doi: 10.1038/ncb1271. Epub 2005 Jun 5.
Epithelial planar cell polarity (PCP) is evident in the cellular organization of many tissues in vertebrates and invertebrates. In mammals, PCP signalling governs convergent extension during gastrulation and the organization of a wide variety of structures, including the orientation of body hair and sensory hair cells of the inner ear. In Drosophila melanogaster, PCP is manifest in adult tissues, including ommatidial arrangement in the compound eye and hair orientation in wing cells. PCP establishment requires the conserved Frizzled/Dishevelled PCP pathway. Mutations in PCP-pathway-associated genes cause aberrant orientation of body hair or inner-ear sensory cells in mice, or misorientation of ommatidia and wing hair in D. melanogaster. Here we provide mechanistic insight into Frizzled/Dishevelled signalling regulation. We show that the ankyrin-repeat protein Diego binds directly to Dishevelled and promotes Frizzled signalling. Dishevelled can also be bound by the Frizzled PCP antagonist Prickle. Strikingly, Diego and Prickle compete with one another for Dishevelled binding, thereby modulating Frizzled/Dishevelled activity and ensuring tight control over Frizzled PCP signalling.
上皮平面细胞极性（PCP）在脊椎动物和无脊椎动物的许多组织的细胞组织中都很明显。在哺乳动物中，PCP信号传导在原肠胚形成过程中控制汇聚延伸以及多种结构的组织，包括体毛的方向和内耳的感觉毛细胞。在果蝇中，PCP表现在成年组织中，包括复眼中小眼的排列和翅细胞中毛的方向。PCP的建立需要保守的卷曲蛋白/散乱蛋白PCP途径。PCP途径相关基因的突变会导致小鼠体毛或内耳感觉细胞的方向异常，或果蝇中小眼和翅毛的方向错误。在这里，我们提供了对卷曲蛋白/散乱蛋白信号调节的机制性见解。我们表明，锚蛋白重复序列蛋白迪戈直接与散乱蛋白结合并促进卷曲蛋白信号传导。散乱蛋白也可以被卷曲蛋白PCP拮抗剂普里克结合。引人注目的是，迪戈和普里克相互竞争与散乱蛋白的结合，从而调节卷曲蛋白/散乱蛋白的活性，并确保对卷曲蛋白PCP信号传导的严格控制。
