β1A Integrin Is a Master Regulator of Invadosome Organization and Function

Mol Biol Cell. 2010 Dec;21(23):4108-19. doi: 10.1091/mbc.E10-07-0580. Epub 2010 Oct 6.

Abstract

Invadosomes are adhesion structures involved in tissue invasion that are characterized by an intense actin polymerization-depolymerization associated with β1 and β3 integrins and coupled to extracellular matrix (ECM) degradation activity. We induced the formation of invadosomes by expressing the constitutive active form of Src, SrcYF, in different cell types. Use of ECM surfaces micropatterned at the subcellular scale clearly showed that in mesenchymal cells, integrin signaling controls invadosome activity. Using β1⁻/⁻ or β3⁻/⁻ cells, it seemed that β1A but not β3 integrins are essential for initiation of invadosome formation. Protein kinase C activity was shown to regulate autoassembly of invadosomes into a ring-like metastructure (rosette), probably by phosphorylation of Ser785 on the β1A tail. Moreover, our study clearly showed that β1A links actin dynamics and ECM degradation in invadosomes. Finally, a new strategy based on fusion of the photosensitizer KillerRed to the β1A cytoplasmic domain allowed specific and immediate loss of function of β1A, resulting in disorganization and disassembly of invadosomes and formation of focal adhesions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Animals
  • Cell Adhesion Molecules / metabolism*
  • Cell Adhesion*
  • Cell Membrane Structures / physiology*
  • Cell Membrane Structures / ultrastructure
  • Cell Movement
  • Cells, Cultured
  • Extracellular Matrix / metabolism
  • Focal Adhesions / metabolism
  • Gene Knockout Techniques
  • Genes, src
  • Integrin beta1 / chemistry
  • Integrin beta1 / metabolism*
  • Integrin beta3 / metabolism
  • Mesoderm / metabolism
  • Mice
  • Phosphorylation
  • Polymerization
  • Protein Kinase C / metabolism
  • Signal Transduction

Substances

  • Actins
  • Cell Adhesion Molecules
  • Integrin beta1
  • Integrin beta3
  • Protein Kinase C