Spatial sensing in fibroblasts mediated by 3' phosphoinositides. Academic Article uri icon

Overview

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 microm(2)/s) and short lifetime of 3' PIs of <1 min. Together, this study suggests that the tyrosine kinase-coupled directional movement of fibroblasts and their radial membrane activity are controlled by local generation and rapid degradation of 3' PI second messengers.

publication date

  • December 11, 2000

Research

keywords

  • Chemotaxis
  • Fibroblasts
  • Phosphatidylinositols
  • Platelet-Derived Growth Factor

Identity

PubMed Central ID

  • PMC2190602

Scopus Document Identifier

  • 0034638836

Digital Object Identifier (DOI)

  • 10.1083/jcb.151.6.1269

PubMed ID

  • 11121441

Additional Document Info

volume

  • 151

issue

  • 6