Laprise Patrick, Beronja Slobodan, Silva-Gagliardi Nancy F, Pellikka Milena, Jensen Abbie M, McGlade C Jane, Tepass Ulrich
Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario M5S 3G5, Canada.
Dev Cell. 2006 Sep;11(3):363-74. doi: 10.1016/j.devcel.2006.06.001.
The Crumbs (Crb) complex is a key regulator of epithelial cell architecture where it promotes apical membrane formation. Here, we show that binding of the FERM protein Yurt to the cytoplasmic domain of Crb is part of a negative-feedback loop that regulates Crb activity. Yurt is predominantly a basolateral protein but is recruited by Crb to apical membranes late during epithelial development. Loss of Yurt causes an expansion of the apical membrane in embryonic epithelia and photoreceptor cells similar to Crb overexpression and in contrast to loss of Crb. Analysis of yurt crb double mutants suggests that these genes function in one pathway and that yurt negatively regulates crb. We also show that the mammalian Yurt orthologs YMO1 and EHM2 bind to mammalian Crb proteins. We propose that Yurt is part of an evolutionary conserved negative-feedback mechanism that restricts Crb complex activity in promoting apical membrane formation.
面包屑（Crb）复合体是上皮细胞结构的关键调节因子，可促进顶端膜的形成。在此，我们表明FERM蛋白Yurt与Crb的细胞质结构域结合是调节Crb活性的负反馈回路的一部分。Yurt主要是一种基底外侧蛋白，但在胚胎上皮发育后期被Crb招募到顶端膜。Yurt缺失会导致胚胎上皮和光感受器细胞中的顶端膜扩张，这与Crb过表达相似，与Crb缺失相反。对yurt crb双突变体的分析表明，这些基因在一条途径中发挥作用，且yurt对crb起负调节作用。我们还表明，哺乳动物Yurt直系同源物YMO1和EHM2与哺乳动物Crb蛋白结合。我们提出，Yurt是一种进化保守的负反馈机制的一部分，该机制在促进顶端膜形成过程中限制Crb复合体的活性。
