title: αII-spectrin regulates invadosome stability and extracellular matrix degradation.
abstract: Invadosomes are actin-rich adhesion structures involved in tissue invasion and extracellular matrix (ECM) remodelling. αII-Spectrin, an ubiquitous scaffolding component of the membrane skeleton and a partner of actin regulators (ABI1, VASP and WASL), accumulates highly and specifically in the invadosomes of multiple cell types, such as mouse embryonic fibroblasts (MEFs) expressing SrcY527F, the constitutively active form of Src or activated HMEC-1 endothelial cells. FRAP and live-imaging analysis revealed that αII-spectrin is a highly dynamic component of invadosomes as actin present in the structures core. Knockdown of αII-spectrin expression destabilizes invadosomes and reduces the ability of the remaining invadosomes to digest the ECM and to promote invasion. The ECM degradation defect observed in spectrin-depleted-cells is associated with highly dynamic and unstable invadosome rings. Moreover, FRAP measurement showed the specific involvement of αII-spectrin in the regulation of the mobile/immobile β3-integrin ratio in invadosomes. Our findings suggest that spectrin could regulate invadosome function and maturation by modulating integrin mobility in the membrane, allowing the normal processes of adhesion, invasion and matrix degradation. Altogether, these data highlight a new function for spectrins in the stability of invadosomes and the coupling between actin regulation and ECM degradation.
authors.affiliation: Institut National de la Transfusion Sanguine, INSERM UMR-S 665, Paris, France, Université Paris 7/Denis Diderot, Paris, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Ponceau
authors.affiliation: Institut Albert Bonniot, Université Joseph Fourier, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale-Université Joseph Fourier U823 Site Santé, Grenoble, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Albigès-Rizo
authors.affiliation: Institut National de la Transfusion Sanguine, INSERM UMR-S 665, Paris, France, Université Paris 7/Denis Diderot, Paris, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Colin-Aronovicz
authors.affiliation: Institut Albert Bonniot, Université Joseph Fourier, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale-Université Joseph Fourier U823 Site Santé, Grenoble, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Destaing
authors.affiliation: Institut National de la Transfusion Sanguine, INSERM UMR-S 665, Paris, France, Université Paris 7/Denis Diderot, Paris, France.
authors.forename: Marie Christine
authors.initials: MC
authors.lastname: Lecomte
mesh_terms: D000818:Animals; D002460:Cell Line; D005109:Extracellular Matrix / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D039661:Integrin beta3 / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D057054:Molecular Imaging; D009154:Mutation; D000069261:Podosomes / Q000378:metabolism*; D055550:Protein Stability; D013049:Spectrin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D039661:Integrin beta3; D013049:Spectrin
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