The non-redundant role of N-WASP in podosome-mediated matrix degradation in macrophages

Leora M. Nusblat, Athanassios Dovas, Dianne Cox

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Wiskott-Aldrich Syndrome Protein (WASP) is a hematopoietic cell-specific regulator of Arp2/3-dependent actin polymerization. Despite the presence of the highly homologous N-WASP (neural-WASP), macrophages from WAS patients are devoid of podosomes, adhesion structures in cells of the monocytic lineage capable of matrix degradation via matrix metalloproteases (MMPs), suggesting that WASP and N-WASP play unique roles in macrophages. To determine whether N-WASP also plays a unique role in macrophage function, N-WASP expression was reduced using silencing RNA in a sub-line of RAW 264.7 macrophages (RAW/LR5). Similar to reduction in WASP levels, cells with reduced N-WASP levels were rounder and less polarized. Interestingly, podosomes still formed when N-WASP was reduced but they were unable to perform matrix degradation. This defect was rescued by re-expression of N-WASP, but not by over-expression of WASP, indicating that these proteins play distinct roles in podosome function. Additionally, reducing N-WASP levels mistargets the metalloprotease MT1-MMP and it no longer localizes to podosomes. However, N-WASP was only found to co-localize with MT1-MMP positive vesicles at podosomes, suggesting that N-WASP may play a role on the targeting or fusion of MMP-containing vesicles to podosomes in macrophage-like cells.

Original languageEnglish (US)
Pages (from-to)205-212
Number of pages8
JournalEuropean Journal of Cell Biology
Volume90
Issue number2-3
DOIs
StatePublished - Feb 1 2011

Keywords

  • Macrophages
  • Matrix degradation
  • Matrix metalloproteases
  • N-WASP
  • Podosomes
  • Vesicle trafficking
  • WASP

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

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