Kumichel Alexandra, Knust Elisabeth
Max-Planck-Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
PLoS One. 2014 Apr 7;9(4):e94038. doi: 10.1371/journal.pone.0094038. eCollection 2014.
The transmembrane protein Crumbs/Crb is a key regulator of apico-basal epithelial cell polarity, both in Drosophila and in vertebrates. In most cases studied so far, the apical localisation of Drosophila Crumbs depends on the interaction of its C-terminal amino acids with the scaffolding protein Stardust. Consequently, embryos lacking either Crumbs or Stardust develop a very similar phenotype, characterised by the loss of epithelial tissue integrity and cell polarity in many epithelia. An exception is the hindgut, which is not affected by the loss of either gene. The hindgut is a single layered epithelial tube composed of two cell populations, the boundary cells and the principal cells. Here we show that Crumbs localisation in the principal cells depends on Stardust, similarly to other embryonic epithelia. In contrast, localisation of Crumbs in the boundary cells does not require Stardust and is independent of its PDZ domain- and FERM-domain binding motifs. In line with this, the considerable upregulation of Crumbs in boundary cells is not followed by a corresponding upregulation of its canonical binding partners. Our data are the first to suggest a mechanism controlling apical Crumbs localisation, which is independent of its conserved FERM- and PDZ-domain binding motifs.
跨膜蛋白Crumb（Crb）是果蝇和脊椎动物中顶-基上皮细胞极性的关键调节因子。在目前研究的大多数情况下，果蝇Crumb的顶端定位取决于其C末端氨基酸与支架蛋白星尘（Stardust）的相互作用。因此，缺乏Crumb或星尘的胚胎会出现非常相似的表型，其特征是许多上皮组织中上皮组织完整性和细胞极性丧失。一个例外是后肠，它不受这两个基因缺失的影响。后肠是一个单层上皮管，由两种细胞群体组成，即边界细胞和主细胞。在这里我们表明，主细胞中Crumb的定位与其他胚胎上皮一样，依赖于星尘。相反，边界细胞中Crumb的定位不需要星尘，并且独立于其PDZ结构域和FERM结构域结合基序。与此一致的是，边界细胞中Crumb的大量上调并没有伴随着其经典结合伴侣的相应上调。我们的数据首次提出了一种控制顶端Crumb定位的机制，该机制独立于其保守的FERM和PDZ结构域结合基序。
