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  • The EMBO Journal (2004) 23, 3758 - 3768
  • doi:10.1038/sj.emboj.7600403

Published online: 23 September 2004

The membrane form of the DNA repair protein Ku interacts at the cell surface with metalloproteinase 9

Sylvie Monferrana, Jenny Pauperta, Stéphanie Dauvillier, Bernard Salles and Catherine Muller

  1. Institut de Pharmacologie et de Biologie Structurale, CNRS UMR 5089, Toulouse, France

Correspondence to:

Bernard Salles, Institut de Pharmacologie et de Biologie Structurale, CNRS UMR 5089, 205 route de Narbonne, 31077 Toulouse Cedex 04, France. Tel.: +33 5 61175936; Fax: +33 5 61175933; E-mail: bernard.salles@ipbs.fr

aThese authors contributed equally to this work

Received 9 October 2003; Accepted 13 August 2004

The Ku heterodimer (Ku70/Ku80) plays a central role in DNA double-strand breaks repair. Ku is also expressed on the cell surface of different types of cells where its function remains poorly understood. From a yeast two-hybrid screen, we have identified a specific interaction between the core region of Ku80 and the hemopexin domain of metalloproteinase 9 (MMP-9), a key enzyme involved in the degradation of extracellular matrix (ECM) components. Ku associates with MMP-9 on the surface of leukemic cells as demonstrated by co-immunoprecipitation experiments in membrane extracts and double-label immunofluorescence studies. In normal and tumoral migratory cells, Ku80 and MMP-9 colocalize at the periphery of leading edge of cells and cellular invasion of collagen IV matrices was blocked by antibodies directed against Ku70 or Ku80 subunits as well as by Ku80-specific antisense oligonucleotides. Our results indicate that Ku and MMP-9 interact at the cell membrane of highly invasive hematopoietic cells of normal and tumoral origin and document the unexpected importance of the membrane-associated form of Ku in the regulation of ECM remodelling.

  • Keywords:

    • extracellular matrix,
    • invasion,
    • ku heterodimer,
    • macrophages,
    • metalloproteinase 9