PAR-1 Kinase Regulates Epithelial Detachment and Directional Protrusion of Migrating Border Cells

Jocelyn A. McDonald, Anna Khodyakova, George Aranjuez, Colleen Dudley, Denise J. Montell

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Many cells that migrate during normal embryonic development or in metastatic cancer first detach from an epithelium. However, this step is often difficult to observe directly in vivo, and the mechanisms controlling the ability of cells to leave the epithelium are poorly understood. In addition, once cells detach, they must assume a migratory phenotype, involving changes in cytoskeletal and signaling dynamics. Drosophila border cells provide a model system in which a combination of forward genetics and live-cell imaging can allow researchers to investigate the cellular and molecular mechanisms of epithelial cell detachment and migration in vivo. Results: We identified the Drosophila homolog of the serine/threonine kinase PAR-1 (MARK/Kin1) in a screen for mutations that disrupt border cell migration. Previous studies identified two proteins, Apontic and Notch, that indirectly affect border cell detachment by regulating transcription of downstream targets. In contrast, PAR-1 directly modulates apical-basal polarity between border cells and epithelial cells to promote detachment. Furthermore, PAR-1, but not the apical polarity complex protein PAR-3, promotes the directionality of transient cell protrusions, which border cells require for sensing the chemoattractant gradient. Conclusions: We conclude that PAR-1-dependent apical-basal polarity is required for proper detachment of migratory border cells from neighboring epithelial cells. Moreover, polarity controlled by PAR-1 influences the ability of migratory cells to sense direction, a critical feature of migration. Thus, this work reveals new insights into two distinct, but essential, steps of epithelial cell migration.

Original languageEnglish (US)
Pages (from-to)1659-1667
Number of pages9
JournalCurrent Biology
Volume18
Issue number21
DOIs
StatePublished - Nov 11 2008

Keywords

  • CELLBIO
  • DEVBIO

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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