Multifaceted control of E-cadherin dynamics by the Adaptor Protein Complex 1 during epithelial morphogenesis

• Published in: Molecular biology of the cell 2022-08, Vol.33 (9), p.mbcE21120598-ar80
• Main Authors: Moreno, Miguel Ramírez, Boswell, Katy, Casbolt, Helen L, Bulgakova, Natalia A
• Format: Article
• Language: English
• Subjects: Analysis; Cadherins; Cell death; Coordination compounds; Drosophila; Identification and classification; Integrins; Membrane proteins; Morphogenesis; Properties; Proteins
• ISSN: 1059-1524; 1939-4586
• DOI: 10.1091/mbc.E21-12-0598

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 cargos. We examined roles of the AP-1 complex in epithelial morphogenesis, using the 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, which 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 tumour-suppressive mechanism. Simultaneously, cells compensate for elevated internalization of E-cadherin by increasing its expression to maintain cell-cell adhesion.