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PMID: 12080346 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A PtdInsP(3)- and Rho GTPase-mediated positive feedback loop regulates neutrophil polarity.

Nature cell biology ·Vol. 4 ·No. 7 ·2002-07-00 ·Pages 509-13

Weiner OD, Neilsen PO, Prestwich GD, Kirschner MW, Cantley LC, Bourne HR

Abstract

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.

MeSH Terms
Animals Cell Polarity/physiology Chemotaxis Dictyostelium/cytology Feedback, Physiological/physiology Fibroblasts/cytology HL-60 Cells Histones/metabolism Humans Neutrophils/cytology Phosphatidylinositol 3-Kinases/metabolism Phosphatidylinositol Phosphates/physiology rho GTP-Binding Proteins/physiology
Chemicals
Histones Phosphatidylinositol Phosphates phosphatidylinositol 3,4,5-triphosphate Phosphatidylinositol 3-Kinases rho GTP-Binding Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Weiner Orion D
Department of Cell Biology, Harvard Medical School and Beth Israel Deaconess Medical Center, 240 Longwood Ave/ C-1, Boston, MA 02115, USA.
Neilsen Paul O
Prestwich Glenn D
Kirschner Marc W
Cantley Lewis C
Bourne Henry R
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Article Info
Journal
Nature cell biology
Abbr.
Nat Cell Biol
ISSN
1465-7392
DOI
10.1038/ncb811
Published
2002-07-00
Pages
509-13
Language
English
Region
England
NLM ID
100890575
PMCID
PMC2823287
Subset
IM
Grants
NIGMS NIH HHS · R01 GM026875 · United States
NINDS NIH HHS · NS29632 · United States
NINDS NIH HHS · R01 NS029632 · United States
NIGMS NIH HHS · R37 GM041890 · United States
NIGMS NIH HHS · R01 GM041890 · United States
NIGMS NIH HHS · R01 GM026875-25 · United States
NIGMS NIH HHS · GM26825 · United States
NIGMS NIH HHS · GM62734-03 · United States
NIGMS NIH HHS · GM41890 · United States
Corrections
CommentIn
PMID: 12105427
External Links
PubMed source DOI: 10.1038/ncb811 PMC Full Text View journal details
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