Spatial sensing in fibroblasts mediated by 3' phosphoinositides

Jason M. Haugh, Franca Codazzi, Mary Teruel, Tobias Meyer

Research output: Contribution to journalArticle

Abstract

The directed movement of fibroblasts towards locally released platelet-derived growth factor (PDGF) is a critical event in wound healing. Although recent studies have implicated polarized activation of phosphoinositide (PI) 3-kinase in G protein-mediated chemotaxis, the role of 3' PI lipids in tyrosine kinase-triggered chemotaxis is not well understood. Using evanescent wave microscopy and green fluorescent protein-tagged Akt pleckstrin homology domain (GFP-AktPH) as a molecular sensor, we show that application of a shallow PDGF gradient triggers a markedly steeper gradient in 3' PI lipids in the adhesion zone of fibroblasts. Polar GFP-AktPH gradients, as well as a new type of radial gradient, were measured from front to rear and from the periphery to the center of the adhesion zone, respectively. A strong spatial correlation between polarized 3' PI production and rapid membrane spreading implicates 3' PI lipids as a direct mediator of polarized migration. Analysis of the temporal changes of 3' PI gradients in the adhesion zone revealed a fast diffusion coefficient (0.5 μm2/s) and short lifetime of 3' PIs of

Original languageEnglish
Pages (from-to)1269-1279
Number of pages11
JournalJournal of Cell Biology
Volume151
Issue number6
DOIs
Publication statusPublished - Dec 11 2000

Keywords

  • Chemotaxis
  • Phosphatidylinositol 3-kinase
  • Platelet-derived growth factor
  • Receptor protein-tyrosine kinases
  • Signal transduction

ASJC Scopus subject areas

  • Cell Biology

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