Brief Communication abstract
Nature Cell Biology 4, 509 - 513 (2002)
Published online: 24 June 2002 | doi:10.1038/ncb811
A PtdInsP3- and Rho GTPase-mediated positive feedback loop regulates neutrophil polarity
Orion D. Weiner1,2, Paul O. Neilsen3, Glenn D. Prestwich4, Marc W. Kirschner1, Lewis C. Cantley2 & Henry R. Bourne5
When presented with a gradient of chemoattractant, many eukaryotic cells respond with polarized accumulation of the phospholipid PtdIns(3,4,5)P3. This lipid asymmetry is one of the earliest readouts of polarity in neutrophils, Dictyostelium discoideum and fibroblasts. However, the mechanisms that regulate PtdInsP3 polarization are not well understood. Using a cationic lipid shuttling system, we have delivered exogenous PtdInsP3 to neutrophils. Exogenous PtdInsP3 elicits accumulation of endogenous PtdInsP3 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 PtdInsP3 polarity in response to both chemoattractant and to exogenous PtdInsP3; it may function through a self-organizing pattern formation system. Emergent properties of positive and negative regulatory links between PtdInsP3 and Rho family GTPases may constitute a broadly conserved module for the establishment of cell polarity during eukaryotic chemotaxis.
- Department of Cell Biology, Harvard Medical School, 240 Longwood Ave/ C-1, Boston, MA 02115, USA
- Department of Cell Biology, Harvard Medical School, Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA
- Echelon Research Laboratories, 420 Chipeta Way, Suite 180, Salt Lake City, UT 84108
- Department of Medicinal Chemistry, University of Utah, 419 Wakara Way, Suite 205, Salt Lake City, UT 84108, USA
- Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143-0450, USA
Correspondence to: Henry R. Bourne5 e-mail: bourne@cmp.ucsf.edu
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