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