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

Area of Science:

• Cell Biology
• Developmental Biology
• Molecular Biology

Background:

• Intracellular trafficking is crucial for distributing transmembrane proteins that control epithelial polarity and adhesion.
• The Adaptor Protein 1 (AP-1) complex is a key regulator of vesicle sorting and cargo binding.

Purpose of the Study:

• To investigate the role of the AP-1 complex in epithelial morphogenesis using the Drosophila wing model.
• To understand how AP-1 influences cell adhesion, polarity, and tissue development.

Main Methods:

• AP-1 complex knockdown in Drosophila wings.
• Analysis of integrin targeting to basal adhesion sites.
• Assessment of cell proliferation and cell death.
• Investigation of E-cadherin localization and internalization.
• Examination of E-cadherin expression levels.

Main Results:

• AP-1 knockdown induced ectopic tissue folding and defects in integrin targeting.
• Loss of AP-1 led to integrin-independent cell death, balancing increased proliferation and preventing hyperplasia.
• A distinct AP-1 pool at adherens junctions was identified.
• AP-1 knockdown caused E-cadherin hyperinternalization from adherens junctions, with enrichment at the Golgi and recycling endosomes.
• E-cadherin hyperinternalization preceded cell death, suggesting a tumor-suppressive role.
• Cells upregulated E-cadherin expression to compensate for increased internalization and maintain adhesion.

Conclusions:

• The AP-1 complex plays a critical role in maintaining epithelial integrity and tissue morphogenesis.
• AP-1 regulates E-cadherin trafficking and localization at adherens junctions.
• E-cadherin hyperinternalization, triggered by AP-1 loss, acts as a tumor-suppressive mechanism by inducing cell death.
• Cellular compensation mechanisms, like increased E-cadherin expression, attempt to preserve cell-cell adhesion.