Journal
NATURE CELL BIOLOGY
Volume 4, Issue 7, Pages 509-512Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb811
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Funding
- NIGMS NIH HHS [R37 GM041890, R01 GM026875, GM41890, R01 GM026875-25, GM26825, GM62734-03, R01 GM041890] Funding Source: Medline
- NINDS NIH HHS [NS29632, R01 NS029632] Funding Source: Medline
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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.
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