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

Cheng han Yu, Nisha Bte Mohd Rafiq, Anitha Krishnasamy, Kevin L. Hartman, Gareth E. Jones, Alexander D. Bershadsky, Michael Sheetz

Research output: Contribution to journalArticle

88 Scopus citations

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 1-2μm), 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.

Original languageEnglish (US)
Pages (from-to)1456-1468
Number of pages13
JournalCell Reports
Volume5
Issue number5
DOIs
StatePublished - Dec 12 2013
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Yu, C. H., Rafiq, N. B. M., Krishnasamy, A., Hartman, K. L., Jones, G. E., Bershadsky, A. D., & Sheetz, M. (2013). Integrin-matrix clusters form podosome-like adhesions in the absence of traction forces. Cell Reports, 5(5), 1456-1468. https://doi.org/10.1016/j.celrep.2013.10.040