2. Academic Validation
  3. Integrin-matrix clusters form podosome-like adhesions in the absence of traction forces

Integrin-matrix clusters form podosome-like adhesions in the absence of traction forces

  • Cell Rep. 2013 Dec 12;5(5):1456-68. doi: 10.1016/j.celrep.2013.10.040.
Cheng-han Yu 1,  Nisha Bte Mohd Rafiq 2,  Anitha Krishnasamy 3,  Kevin L Hartman 3,  Gareth E Jones 4,  Alexander D Bershadsky 5,  Michael P Sheetz 6
Affiliations

Affiliations

  • 1 Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore. Electronic address: chyu@nus.edu.sg.
  • 2 Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore; Randall Division of Cell & Molecular Biophysics, King's College London, London SE1 1UL, UK.
  • 3 Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
  • 4 Randall Division of Cell & Molecular Biophysics, King's College London, London SE1 1UL, UK.
  • 5 Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
  • 6 Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore; Department of Biological Sciences, Columbia University, New York, NY, 10027, USA. Electronic address: ms2001@columbia.edu.
PMID: 24290759 DOI: 10.1016/j.celrep.2013.10.040
Abstract

Matrix-activated integrins can form different adhesion structures. We report that nontransformed fibroblasts develop podosome-like adhesions when spread on fluid Arg-Gly-Asp peptide (RGD)-lipid surfaces, whereas they habitually form focal adhesions on rigid RGD glass surfaces. Similar to classic macrophage podosomes, the podosome-like adhesions are protrusive and characterized by doughnut-shaped RGD rings that surround characteristic core components including F-actin, N-WASP, and Arp2/Arp3. Furthermore, there are 18 podosome markers in these adhesions, though they lack Matrix Metalloproteinases that characterize invadopodia and podosomes of Src-transformed cells. When nontransformed cells develop force on integrin-RGD clusters by pulling RGD lipids to prefabricated rigid barriers (metal lines spaced by 1-2 μm), these podosomes fail to form and instead form focal adhesions. The formation of podosomes on fluid surfaces is mediated by local activation of phosphoinositide 3-kinase (PI3K) and the production of phosphatidylinositol-(3,4,5)-triphosphate (PIP3) in a FAK/PYK2-dependent manner. Enrichment of PIP3 precedes N-WASP activation and the recruitment of RhoA-GAP ARAP3. We propose that adhesion structures can be modulated by traction force development and that production of PIP3 stimulates podosome formation and subsequent RhoA downregulation in the absence of traction force.

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