Intracellular trafficking regulates the distribution of transmembrane proteins including the key determinants of epithelial polarity and adhesion. The Adaptor Protein 1 (AP-1) complex is the key regulator of vesicle sorting, which binds a large number of specific cargos. We examined roles of the AP-1 complex in epithelial morphogenesis, using the Drosophila wing as a paradigm. We found that AP-1 knockdown leads to ectopic folds caused by trafficking defects of integrins. This occurs concurrently with an increase in the apical cell area and induction of cell death due to defects in E-cadherin trafficking. We discovered a distinct pool of AP-1 localizes at the apical Adherens Junctions, where it limits internalization of E-cadherin from the cell surface. Upon AP-1 knockdown, the accompanying hyperinternalization of E-cadherin induces cell death by an uncharacterised mechanism with a potential tumour-suppressive role. Simultaneously, cells increase expression of E-cadherin in a compensatory mechanism to maintain cell-cell adhesion.

中文翻译：

---

衔接蛋白复合物1限制上皮形态发生过程中E-钙粘蛋白内吞

细胞内运输调节跨膜蛋白的分布，包括上皮极性和粘附的关键决定因素。衔接蛋白1（AP-1）复合物是囊泡分选的关键调节剂，可结合大量特定货物。我们使用果蝇翼为范例，研究了AP-1复合物在上皮形态发生中的作用。我们发现，AP-1敲低导致整联蛋白运输缺陷引起的异位折叠。这与由于E-钙粘蛋白运输中的缺陷导致的顶细胞面积增加和诱导细胞死亡同时发生。我们发现了一个独特的AP-1池位于顶点的Adherens交界处，它限制了E-钙粘蛋白从细胞表面的内在化。在AP-1击倒后，随之而来的E-钙粘蛋白过度内在化通过未知机制诱导细胞死亡，该机制具有潜在的肿瘤抑制作用。同时，细胞以补偿机制增加E-钙黏着蛋白的表达，以维持细胞与细胞的粘附。