Novel function for AP-1B during cell migration

Area of Science:

• Cell Biology
• Molecular Biology
• Cancer Research

Background:

• The epithelial cell-specific clathrin adaptor protein (AP)-1B mediates cargo sorting to the basolateral membrane.
• β1 integrin and autosomal recessive hypercholesterolemia protein (ARH) are involved in cellular processes.

Purpose of the Study:

• To investigate the role of AP-1B in β1 integrin sorting and its function during epithelial cell migration.
• To explore the novel localization and function of AP-1B at the basal plasma membrane.

Main Methods:

• Confocal microscopy and total internal reflection fluorescence microscopy to visualize AP-1B and β1 integrin colocalization.
• Stochastic optical reconstruction microscopy and immunoelectron microscopy to identify AP-1B structures at the basal plasma membrane.
• Quantitative real-time reverse transcription PCR to analyze AP-1B expression in cancer cell lines.

Main Results:

• β1 integrin sorting to the basolateral membrane depends on AP-1B and ARH.
• AP-1B localizes to focal adhesions and basal plasma membrane structures during cell migration.
• AP-1B expression is reduced in highly migratory metastatic cancer cells.
• AP-1B and ARH expression slowed epithelial cell migration during wound healing.

Conclusions:

• AP-1B has an unprecedented role at the basal plasma membrane during collective epithelial cell migration.
• The novel function of AP-1B in cell migration may represent an anticancer mechanism, as its expression is lost in metastatic cancer.