ArticleThe Journal of cell biology2000
Mechanism of N-WASP activation by CDC42 and phosphatidylinositol 4, 5-bisphosphate.
Article in The Journal of cell biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 242 papers.
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Who cites it
242 citing papers in PubMed, 630 citations in OpenAlex.
- α-Parvin regulation of cell rearrangement is critical for ureteric bud branching morphogenesis.Science advances · 2026Article
- Systematic AI-assisted screening of the cadhesome to map epithelial monolayer mechanics.Cell communication and signaling : CCS · 2026Article
- Distinct impact of PI(4)P flux on PI(4,5)PProceedings of the National Academy of Sciences of the United States of America · 2026Article
- One-step purification of a bioactive PAK1-derived peptide.Analytical biochemistry · 2026Article
- Membrane curvature initiates Cdc42-FBP17-N-WASP clustering and actin nucleation.The EMBO journal · 2026Article
- Article
- Immunological synapse: structures, molecular mechanisms and therapeutic implications in disease.Signal transduction and targeted therapy · 2025Review
- PI(4,5)PBiochimica et biophysica acta. Molecular and cell biology of lipids · 2025Review
- The DNA Repair Component EEPD1 Regulates Actin Polymerization.Biology of the cell · 2025Article
- Morphological control of merlin-Rac antagonism in proliferation-promoting signaling.Science signaling · 2025Article
- Membrane Association of Intrinsically Disordered Proteins.Annual review of biophysics · 2025Review
- Tristetraprolin affects invasion-associated genes expression and cell motility in triple-negative breast cancer model.Cytoskeleton (Hoboken, N.J.) · 2025Article
- Phosphoinositide signaling at the cytoskeleton in the regulation of cell dynamics.Cell death & disease · 2025Review
- PI(3,4,5)P3-mediated Cdc42 activation regulates macrophage podosome assembly.Cellular and molecular life sciences : CMLS · 2025Article
- Review
- Actin polymerization counteracts prewetting of N-WASP on supported lipid bilayers.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Adaptor protein Abelson interactor 1 in homeostasis and disease.Cell communication and signaling : CCS · 2024Review
- Competition and synergy of Arp2/3 and formins in nucleating actin waves.Cell reports · 2024Article
- The concerted action of SEPT9 and EPLIN modulates the adhesion and migration of human fibroblasts.Life science alliance · 2024Article
- Inverted apicobasal polarity in health and disease.Journal of cell science · 2024Review
182 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Neuronal Wiskott-Aldrich Syndrome protein (N-WASP) transmits signals from Cdc42 to the nucleation of actin filaments by Arp2/3 complex. Although full-length N-WASP is a weak activator of Arp2/3 complex, its activity can be enhanced by upstream regulators such as Cdc42 and PI(4,5)P(2). We dissected this activation reaction and found that the previously described physical interaction between the NH(2)-terminal domain and the COOH-terminal effector domain of N-WASP is a regulatory interaction because it can inhibit the actin nucleation activity of the effector domain by occluding the Arp2/3 binding site. This interaction between the NH(2)- and COOH termini must be intramolecular because in solution N-WASP is a monomer. Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) influences the activity of N-WASP through a conserved basic sequence element located near the Cdc42 binding site rather than through the WASp homology domain 1. Like Cdc42, PI(4,5)P(2) reduces the affinity between the NH(2)- and COOH termini of the molecule. The use of a mutant N-WASP molecule lacking this basic stretch allowed us to delineate a signaling pathway in Xenopus extracts leading from PI(4, 5)P(2) to actin nucleation through Cdc42, N-WASP, and Arp2/3 complex. In this pathway, PI(4,5)P(2) serves two functions: first, as an activator of N-WASP; and second, as an indirect activator of 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.