Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, and the Graduate Program in Molecular and Developmental Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Dev Biol. 2011 Dec 1;360(1):87-95. doi: 10.1016/j.ydbio.2011.09.009. Epub 2011 Sep 19.
Epithelial cells are characterized by an "apical-basal" polarization. The transmembrane protein Crumbs (Crb) is an essential apical determinant which confers apical membrane identity. Previous studies indicated that Crb did not constantly reside on the apical membrane, but was actively recycled. However, the cellular mechanism(s) underlying this process was unclear. Here we showed that in Drosophila, retromer, which was a retrograde complex recycling certain transmembrane proteins from endosomes to trans-Golgi network (TGN), regulated Crb in epithelial cells. In the absence of retromer, Crb was mis-targeted into lysosomes and degraded, causing a disruption of the apical-basal polarity. We further showed that Crb co-localized and interacted with retromer, suggesting that retromer regulated the retrograde recycling of Crb. Our data presented here uncover the role of retromer in regulating apical-basal polarity in epithelial cells and identify retromer as a novel regulator of Crb recycling.
上皮细胞的特征是具有“顶底”极性。跨膜蛋白 Crumbs（Crb）是一种必需的顶端决定因素，赋予顶端膜的特性。先前的研究表明，Crb 不会一直位于顶端膜上，而是被积极地回收利用。然而，这一过程背后的细胞机制尚不清楚。在这里，我们发现在果蝇中，retromer（一种从内体将某些跨膜蛋白逆行运输到 TGN 的逆行复合物）调节上皮细胞中的 Crb。在没有 retromer 的情况下，Crb 被错误地靶向到溶酶体并降解，导致顶底极性的破坏。我们进一步表明，Crb 与 retromer 共定位并相互作用，表明 retromer 调节 Crb 的逆行回收。我们这里提供的数据揭示了 retromer 在调节上皮细胞顶底极性中的作用，并确定 retromer 是 Crb 回收的新型调节剂。
