The cortactin-binding domain of WIP is essential for podosome formation and extracellular matrix degradation by murine dendritic cells

Inmaculada Bañón-Rodríguez, James Monypenny, Chiara Ragazzini, Ana Franco, Yolanda Calle, Gareth E Jones, Inés M Antón

Research output: Contribution to journalArticlepeer-review


In immature dendritic cells (DCs) podosomes form and turn over behind the leading edge of migrating cells. The Arp2/3 complex activator Wiskott-Aldrich Syndrome Protein (WASP) localises to the actin core of forming podosomes together with WASP-Interacting Protein (WIP). A second weaker Arp2/3 activator, cortactin, is also found at podosomes where it has been proposed to participate in matrix metalloproteinase (MMP) secretion. We have previously shown that WIP(-/-) DCs are unable to make podosomes. WIP binds to cortactin and in this report we address whether WIP regulates cortactin-mediated MMP activity. Using DCs derived from splenic murine precursors, we found that wild-type cells were able to localise MMPs at podosomes where matrix degradation takes place. In contrast, WIP(-/-) DCs remain able to synthesise MMPs but do not degrade the extracellular matrix. Infection of WIP KO DCs with lentivirus expressing WIP restored both podosome formation and their ability to degrade the extracellular matrix, implicating WIP-induced podosomes as foci of functional MMP location. When WIP KO DCs were infected with a mutant form of WIP lacking the cortactin-binding domain (WIPΔ110-170) DCs were only able to elaborate disorganised podosomes that were unable to support MMP-mediated matrix degradation. Taken together, these results suggest a role for WIP not only in WASP-mediated actin polymerisation and podosome formation, but also in cortactin-mediated extracellular matrix degradation by MMPs.

Original languageEnglish
Pages (from-to)213-23
Number of pages11
JournalEuropean Journal of Cell Biology
Issue number2-3
Publication statusPublished - 19 Oct 2010


  • Animals
  • Carrier Proteins
  • Cell Line, Tumor
  • Cell Surface Extensions
  • Cortactin
  • Dendritic Cells
  • Enzyme Precursors
  • Extracellular Matrix
  • Fibronectins
  • Gelatinases
  • Humans
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Mice
  • Mice, Knockout
  • Protein Binding
  • Protein Structure, Tertiary

Cite this