Sasaki Nobuo, Sasamura Takeshi, Ishikawa Hiroyuki O, Kanai Maiko, Ueda Ryu, Saigo Kaoru, Matsuno Kenji
Department of Biological Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
Genes Cells. 2007 Jan;12(1):89-103. doi: 10.1111/j.1365-2443.2007.01037.x.
Notch (N) and its ligands, Delta (Dl) and Serrate (Ser), are transmembrane proteins that mediate the cell-cell interactions necessary for many cell-fate decisions. In Drosophila, N is predominantly localized to the apical portion of epithelial cells, but the mechanisms and functions of this localization are unknown. Here, we found N, Dl, and Ser were mostly located in the region from the subapical complex (SAC) to the apical portion of the adherens junctions (AJs) in wing disc epithelium. N was delivered to the SAC/AJs in two phases. First, polarized exocytosis specifically delivered nascent N to the apical plasma membrane and AJs in an O-fut1-independent manner. Second, N at the plasma membrane was relocated to the SAC/AJs by Dynamin- and Rab5-dependent transcytosis; this step required the O-fut1 function. Disruption of the apical polarity by Drosophila E-cadherin (DEcad) knock down caused N and Dl localization to the SAC/AJs to fail. N, but not Dl, formed a specific complex with DEcad in vivo. Finally, our results suggest that juxtacrine signaling in epithelia generally depends on the apicobasally polarized structure of epithelial cells.
Notch（N）及其配体Delta（Dl）和锯齿蛋白（Ser）是跨膜蛋白，介导许多细胞命运决定所必需的细胞间相互作用。在果蝇中，N主要定位于上皮细胞的顶端部分，但其定位的机制和功能尚不清楚。在这里，我们发现N、Dl和Ser大多位于翅芽上皮中从亚顶端复合体（SAC）到黏着连接（AJs）顶端部分的区域。N分两个阶段被递送至SAC/AJs。首先，极化胞吐作用以不依赖O-fut1的方式将新生的N特异性地递送至顶端质膜和AJs。其次，质膜上的N通过动力蛋白和Rab5依赖的转胞吞作用重新定位到SAC/AJs；这一步骤需要O-fut1的功能。果蝇E-钙黏蛋白（DEcad）敲低导致顶端极性破坏，致使N和Dl在SAC/AJs处的定位失败。在体内，N而非Dl与DEcad形成特定复合物。最后，我们的结果表明上皮细胞中的旁分泌信号传导通常依赖于上皮细胞的顶基极化结构。
