ArticleMolecular biology of the cell2009
Cdc42 regulates Fc gamma receptor-mediated phagocytosis through the activation and phosphorylation of Wiskott-Aldrich syndrome protein (WASP) and neural-WASP.
Article in Molecular biology of the cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 120 citations in OpenAlex.
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- Molecular Dynamics of Trogocytosis and Other Contact-Dependent Cell Trafficking Mechanisms in Tumor Pathogenesis.Cancers · 2025Review
- CDC42 Regulates the ERK Pathway to Improve Oxygen‒Glucose Deprivation/Reoxygenation-Induced Neural Oxidative Stress and Apoptosis.Molecular neurobiology · 2025Article
- Measurement of macrophage phagocytic capacity by quantifying maximum membrane extension using an opsonized capillary tube assay.Scientific reports · 2025Article
- Phagocytosis.Methods in molecular biology (Clifton, N.J.) · 2024Review
- Propulsive cell entry diverts pathogens from immune degradation by remodeling the phagocytic synapse.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- DOCK8 is essential for neutrophil mediated clearance of cutaneous S. aureus infection.Clinical immunology (Orlando, Fla.) · 2023Article
- Endocytosis in cancer and cancer therapy.Nature reviews. Cancer · 2023Review
- Propulsive cell entry diverts pathogens from immune degradation by remodeling the phagocytic synapse.bioRxiv : the preprint server for biology · 2023Article
- Profiling Chromatin Accessibility Responses in Goat Bronchial Epithelial Cells Infected withInternational journal of molecular sciences · 2023Article
- Efferocytosis: An Emerging Therapeutic Strategy for Type 2 Diabetes Mellitus and Diabetes Complications.Journal of inflammation research · 2023Review
- Spatial models of pattern formation during phagocytosis.PLoS computational biology · 2022Article
- Emerging Concepts in Defective Macrophage Phagocytosis in Cystic Fibrosis.International journal of molecular sciences · 2022Review
- Wasl is crucial to maintain microglial core activities during glioblastoma initiation stages.Glia · 2022Article
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- Proteome Profiling of PMJ2-R and Primary Peritoneal Macrophages.International journal of molecular sciences · 2021Article
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- Better Together: Current Insights Into Phagosome-Lysosome Fusion.Frontiers in immunology · 2021Review
- Monitoring Phosphoinositide Fluxes and Effectors During Leukocyte Chemotaxis and Phagocytosis.Frontiers in cell and developmental biology · 2021Review
11 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Cdc42 is a key regulator of the actin cytoskeleton and activator of Wiskott-Aldrich syndrome protein (WASP). Although several studies have separately demonstrated the requirement for both Cdc42 and WASP in Fc(gamma) receptor (Fc(gamma)R)-mediated phagocytosis, their precise roles in the signal cascade leading to engulfment are still unclear. Reduction of endogenous Cdc42 expression by using RNA-mediated interference (short hairpin RNA [shRNA]) severely impaired the phagocytic capacity of RAW/LR5 macrophages, due to defects in phagocytic cup formation, actin assembly, and pseudopod extension. Addition of wiskostatin, a WASP/neural-WASP (N-WASP) inhibitor showed extensive inhibition of phagocytosis, actin assembly, and cell extension identical to the phenotype seen upon reduction of Cdc42 expression. However, using WASP-deficient bone marrow-derived macrophages or shRNA of WASP or N-WASP indicated a requirement for both WASP and N-WASP in phagocytosis. Cdc42 was necessary for WASP/N-WASP activation, as determined using a conformation-sensitive antibody against WASP/N-WASP and partial restoration of phagocytosis in Cdc42 reduced cells by expression of a constitutively activated WASP. In addition, Cdc42 was required for proper WASP tyrosine phosphorylation, which was also necessary for phagocytosis. These results indicate that Cdc42 is essential for the activation of WASP and N-WASP, leading to actin assembly and phagocytic cup formation by macrophages during Fc(gamma)R-mediated phagocytosis.
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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.