Multifaceted control of E-cadherin dynamics by Adaptor Protein Complex 1 during epithelial morphogenesis.
Multifaceted control of E-cadherin dynamics by Adaptor Protein Complex 1 during epithelial morphogenesis.
复制标题
DOI：
10.1091/mbc.e21-12-0598
复制
发表时间：
2022-08-01
影响因子：
3.3
通讯作者：
Bulgakova NA
中科院分区：
文献类型：
--
作者：
Moreno MR;Boswell K;Casbolt HL;Bulgakova NA
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。接头蛋白1 （AP-1）复合体是囊泡分选的关键调节因子，它结合许多特定的货物。我们以果蝇翅膀为例，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敲低导致异位组织折叠，这与观察到的整合素靶向基底细胞-细胞外基质粘附位点的缺陷是一致的。这与不依赖整合素的细胞死亡诱导同时发生，从而抵消增殖升高并防止增生。我们发现了一个独特的AP-1库，它位于根尖下粘附体连接处。AP-1被敲除后，e -钙粘蛋白从这些连接处过度内化，并在高尔基体和循环核内体中富集。然后，我们提供证据表明，e -钙粘蛋白超内化在潜在的肿瘤抑制机制中作用于细胞死亡的上游。同时，细胞通过增加e -钙粘蛋白的表达来补偿e -钙粘蛋白内化的升高，以维持细胞间的粘附。
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 many specific cargoes. 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 tissue folding, which is consistent with the observed defects in integrin targeting to the basal cell–extracellular matrix adhesion sites. This occurs concurrently with an integrin-independent induction of cell death, which counteracts elevated proliferation and prevents hyperplasia. We discovered a distinct pool of AP-1 that localizes at the subapical adherens junctions. Upon AP-1 knockdown, E-cadherin is hyperinternalized from these junctions and becomes enriched at the Golgi and recycling endosomes. We then provide evidence that E-cadherin hyperinternalization acts upstream of cell death in a potential tumor-suppressive mechanism. Simultaneously, cells compensate for elevated internalization of E-cadherin by increasing its expression to maintain cell–cell adhesion.
影响因子：
4.6
作者：
Sauvageau E;McCormick PJ;Lefrancois S
通讯作者：
Lefrancois S