RRC ID 74734
Author Moreno MR, Boswell K, Casbolt HL, Bulgakova NA.
Title Multifaceted control of E-cadherin dynamics by Adaptor Protein Complex 1 during epithelial morphogenesis.
Journal Mol Biol Cell
Abstract 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.
Volume 33(9)
Pages ar80
Published 2022-8-1
DOI 10.1091/mbc.E21-12-0598
PMID 35609212
PMC PMC9582639
MeSH Adaptor Protein Complex 1* / metabolism Adherens Junctions / metabolism Animals Cadherins / metabolism Cell Polarity Drosophila / metabolism Epithelial Cells / metabolism Integrins / metabolism Morphogenesis / physiology Protein Transport / physiology Transcription Factor AP-1* / metabolism
IF 3.791
Drosophila DGRC#109007