Novel function for AP-1B during cell migration

Margaret Johnson Kell, Su Fen Ang, Lucy Pigati, Abby Halpern, Heike Fölsch*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The epithelial cell-specific clathrin adaptor protein (AP)-1B has a well-established role in polarized sorting of cargos to the basolateral membrane. Here we show that β1 integrin was dependent on AP-1B and its coadaptor, autosomal recessive hypercholesterolemia protein (ARH), for sorting to the basolateral membrane. We further demonstrate an unprecedented role for AP-1B at the basal plasma membrane during collective cell migration of epithelial sheets. During wound healing, expression of AP-1B (and ARH in AP–1B-positive cells) slowed epithelial-cell migration. We show that AP-1B colocalized with β1 integrin in focal adhesions during cell migration using confocal microscopy and total internal reflection fluorescence microscopy on fixed specimens. Further, AP-1B labeling in cell protrusions was distinct from labeling for the endocytic adaptor complex AP-2. Using stochastic optical reconstruction microscopy we identified numerous AP–1B-coated structures at or close to the basal plasma membrane in cell protrusions. In addition, immunoelectron microscopy showed AP-1B in coated pits and vesicles at the plasma membrane during cell migration. Lastly, quantitative real-time reverse transcription PCR analysis of human epithelial-derived cell lines revealed a loss of AP-1B expression in highly migratory metastatic cancer cells suggesting that AP-1B’s novel role at the basal plasma membrane during cell migration might be an anticancer mechanism.

Original languageEnglish (US)
Pages (from-to)2475-2493
Number of pages19
JournalMolecular biology of the cell
Volume31
Issue number22
DOIs
StatePublished - Oct 2020

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Novel function for AP-1B during cell migration'. Together they form a unique fingerprint.

Cite this