ArticleThe Journal of cell biology2003
Rac and Cdc42 play distinct roles in regulating PI(3,4,5)P3 and polarity during neutrophil chemotaxis.
Article in The Journal of cell biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 223 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
223 citing papers in PubMed, 480 citations in OpenAlex.
- The actin regulatory protein HS1 interacts with Arp2/3 and mediates efficient neutrophil chemotaxis.The Journal of biological chemistry · 2012Trial
- A phase field model with stochastic input simulates cellular gradient sensing, morphodynamics, and fidelity of haptotaxis.PLoS computational biology · 2026Article
- Reconstitution of Ras-PI3Kγ membrane communication and feedback using light-induced signaling inputs.Nature communications · 2026Article
- A phase field model with stochastic input simulates cellular gradient sensing, morphodynamics, and fidelity of haptotaxis.bioRxiv : the preprint server for biology · 2026Article
- Polyploidy and Senescence of Cancer Cells: Impact of Cell Fusion.Advances in experimental medicine and biology · 2026Review
- CD47 inhibits phagocytosis through Vav dephosphorylation.The Journal of cell biology · 2025Article
- The nuclear phosphoinositide-p53 signalosome in the regulation of cell motility.Protein & cell · 2025Review
- Orchestrating movement: the role of Caveolin-1 in migration and metastasis.Molecular cancer · 2025Review
- Spatial distribution of cytoskeleton-mediated feedback controls cell polarization: A computational study.PLoS computational biology · 2025Article
- Complementary cytoskeletal feedback loops control signal transduction excitability and cell polarity.Nature communications · 2025Article
- Competing signaling pathways controls electrotaxis.iScience · 2025Article
- Spatial distribution of cytoskeleton-mediated feedback controls cell polarization: a computational study.bioRxiv : the preprint server for biology · 2025Article
- Phosphoinositide signalling in cell motility and adhesion.Nature cell biology · 2025Review
- Phosphoinositide signaling at the cytoskeleton in the regulation of cell dynamics.Cell death & disease · 2025Review
- The Protein Kinase aPKC as Well as the Small GTPases RhoA and Cdc42 Regulates Neutrophil Chemotaxis Partly by Recruiting the ROCK Kinase to the Leading Edge.Genes to cells : devoted to molecular & cellular mechanisms · 2025Article
- Article
- Traveling-wave chemotaxis of neutrophil-like HL-60 cells.Molecular biology of the cell · 2025Article
- A high-throughput chemotaxis assay for assessing immunotoxicity using multiple human immune cell types.NAM journal · 2025Article
- Oscillatory dynamics of Rac1 activity in Dictyostelium discoideum amoebae.PLoS computational biology · 2024Article
- Distinct mechanisms regulate ventricular and atrial chamber wall formation.Nature communications · 2024Article
163 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Neutrophils exposed to chemoattractants polarize and accumulate polymerized actin at the leading edge. In neutrophil-like HL-60 cells, this asymmetry depends on a positive feedback loop in which accumulation of a membrane lipid, phosphatidylinositol (PI) 3,4,5-trisphosphate (PI[3,4,5]P3), leads to activation of Rac and/or Cdc42, and vice versa. We now report that Rac and Cdc42 play distinct roles in regulating this asymmetry. In the absence of chemoattractant, expression of constitutively active Rac stimulates accumulation at the plasma membrane of actin polymers and of GFP-tagged fluorescent probes for PI(3,4,5)P3 (the PH domain of Akt) and activated Rac (the p21-binding domain of p21-activated kinase). Dominant negative Rac inhibits chemoattractant-stimulated accumulation of actin polymers and membrane translocation of both fluorescent probes and attainment of morphologic polarity. Expression of constitutively active Cdc42 or of two different protein inhibitors of Cdc42 fails to mimic effects of the Rac mutants on actin or PI(3,4,5)P3. Instead, Cdc42 inhibitors prevent cells from maintaining a persistent leading edge and frequently induce formation of multiple, short lived leading edges containing actin polymers, PI(3,4,5)P3, and activated Rac. We conclude that Rac plays a dominant role in the PI(3,4,5)P3-dependent positive feedback loop required for forming a leading edge, whereas location and stability of the leading edge are regulated by Cdc42.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.