CSF-1 and PI 3-kinase regulate podosome distribution and assembly in macrophages

Ann P Wheeler, Stephen D Smith, Anne J Ridley

Research output: Contribution to journalArticlepeer-review

Abstract

Podosomes are actin-rich adhesive foci found in several cell types, including macrophages. They have a core containing actin and actin-binding proteins and a peripheral ring of integrins and associated proteins. We show that podosomes are abundant in polarized mouse bone marrow-derived macrophages (BMM) and are found primarily in lamellae. We investigated the effects of CSF-1, which induces membrane ruffling, cell spreading, and subsequent polarization and migration, on podosome formation. CSF-1 induces a transient increase in podosome number and enhances the formation of circular arrays of podosomes. Conversely, CSF-1 withdrawal leads to a reduction in podosomes and a decrease in polarized cells. The PI 3-kinase inhibitor LY294002 induces loss of podosomes together with rapid retraction of lamellae and loss of polarity. Our results indicate that CSF-1 acts via PI 3-kinase to enhance podosome assembly and that this is linked to macrophage polarization.

Original languageEnglish
Pages (from-to)132-40
Number of pages9
JournalCell motility and the cytoskeleton
Volume63
Issue number3
DOIs
Publication statusPublished - Mar 2006

Keywords

  • Animals
  • Cells, Cultured
  • Macrophage Colony-Stimulating Factor
  • Macrophages
  • Mice
  • Mice, Inbred C57BL
  • Phosphatidylinositol 3-Kinases

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