A PtdInsP3- and Rho GTPase-mediated positive feedback loop regulates neutrophil polarity Academic Article uri icon


MeSH Major

  • Cell Polarity
  • Feedback, Physiological
  • Neutrophils
  • Phosphatidylinositol Phosphates
  • rho GTP-Binding Proteins


  • When presented with a gradient of chemoattractant, many eukaryotic cells respond with polarized accumulation of the phospholipid PtdIns(3,4,5)P(3). This lipid asymmetry is one of the earliest readouts of polarity in neutrophils, Dictyostelium discoideum and fibroblasts. However, the mechanisms that regulate PtdInsP(3) polarization are not well understood. Using a cationic lipid shuttling system, we have delivered exogenous PtdInsP(3) to neutrophils. Exogenous PtdInsP(3) elicits accumulation of endogenous PtdInsP(3) in a positive feedback loop that requires endogenous phosphatidylinositol-3-OH kinases (PI(3)Ks) and Rho family GTPases. This feedback loop is important for establishing PtdInsP(3) polarity in response to both chemoattractant and to exogenous PtdInsP(3); it may function through a self-organizing pattern formation system. Emergent properties of positive and negative regulatory links between PtdInsP(3) and Rho family GTPases may constitute a broadly conserved module for the establishment of cell polarity during eukaryotic chemotaxis.

publication date

  • July 22, 2002



  • Academic Article



  • eng

PubMed Central ID

  • PMC2823287

Digital Object Identifier (DOI)

  • 10.1038/ncb811

PubMed ID

  • 12080346

Additional Document Info

start page

  • 509

end page

  • 13


  • 4


  • 7