The Adaptor Protein Complex 1 limits E-cadherin endocytosis during epithelial morphogenesis
The Adaptor Protein Complex 1 limits E-cadherin endocytosis during epithelial morphogenesis
复制标题
DOI：
10.1101/2020.10.14.340372
复制
发表时间：
2020-10
期刊：
影响因子：
--
通讯作者：
M. Moreno;K. Boswell;N. Bulgakova
中科院分区：
文献类型：
--
作者：
M. Moreno;K. Boswell;N. Bulgakova
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因子，它结合大量特定的货物。我们研究了AP-1复合物在上皮形态发生中的作用，以果蝇翅膀为范例。我们发现，AP-1敲低导致异位折叠所造成的运输缺陷的整合素。这与由于E-钙粘蛋白运输缺陷引起的顶端细胞面积增加和细胞死亡诱导同时发生。我们发现了一个独特的AP-1池定位在顶端粘附连接，在那里它限制了细胞表面的E-钙粘蛋白的内化。在AP-1敲低后，伴随的E-钙粘蛋白的过度内化通过具有潜在肿瘤抑制作用的未表征机制诱导细胞死亡。同时，细胞通过代偿机制增加E-钙粘蛋白的表达以维持细胞间粘附。
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.