β1A Integrin Is a Master Regulator of Invadosome Organization and Function

Invadosomes are adhesion structures involved in tissue invasion that are characterized by an intense actin polymerization-depolymerization associated with beta 1 and beta 3 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 beta 1(-/-) or beta 3(-/-) cells, it seemed that beta 1A but not beta 3 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 beta 1A tail. Moreover, our study clearly showed that beta 1A links actin dynamics and ECM degradation in invadosomes. Finally, a new strategy based on fusion of the photosensitizer KillerRed to the beta 1A cytoplasmic domain allowed specific and immediate loss of function of beta 1A, resulting in disorganization and disassembly of invadosomes and formation of focal adhesions.