ArticleThe Journal of biological chemistry2012
Ras-related GTPases Rap1 and RhoA collectively induce the phagocytosis of serum-opsonized zymosan particles in macrophages.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 50 citations in OpenAlex.
- RAP1-RHO small GTPase cross-talk mediates integrindependent and -independent platelet procoagulant response.Haematologica · 2026Article
- Regulating white blood cell activity through the novel universal receptive system.Scientific reports · 2025Article
- Review
- SILAC-based quantitative proteomics to investigate the eicosanoid associated inflammatory response in activated macrophages.Journal of inflammation (London, England) · 2022Article
- Emerging Concepts in Defective Macrophage Phagocytosis in Cystic Fibrosis.International journal of molecular sciences · 2022Review
- Profilin: many facets of a small protein.Biophysical reviews · 2020Review
- Profilin choreographs actin and microtubules in cells and cancer.International review of cell and molecular biology · 2020Article
- Review
- Article
- Phagocytic Roles of Glial Cells in Healthy and Diseased Brains.Biomolecules & therapeutics · 2018Review
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- The role of small GTPases and EPAC-Rap signaling in the regulation of the blood-brain and blood-retinal barriers.Tissue barriers · 2017Review
- Novel Resolvin D2 Receptor Axis in Infectious Inflammation.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Phagocytosis: A Fundamental Process in Immunity.BioMed research international · 2017Review
- Apoptotic cell recognition receptors and scavenger receptors.Immunological reviews · 2016Review
- The established and emerging roles of astrocytes and microglia in amyotrophic lateral sclerosis and frontotemporal dementia.Frontiers in cellular neuroscience · 2015Review
- Coxiella burnetii Phagocytosis Is Regulated by GTPases of the Rho Family and the RhoA Effectors mDia1 and ROCK.PloS one · 2015Article
- Comparison of potato and asian citrus psyllid adult and nymph transcriptomes identified vector transcripts with potential involvement in circulative, propagative liberibacter transmission.Pathogens (Basel, Switzerland) · 2014Article
- Streptococcus pneumoniae ClpL modulates adherence to A549 human lung cells through Rap1/Rac1 activation.Infection and immunity · 2014Article
- IκB kinase γ/nuclear factor-κB-essential modulator (IKKγ/NEMO) facilitates RhoA GTPase activation, which, in turn, activates Rho-associated KINASE (ROCK) to phosphorylate IKKβ in response to transforming growth factor (TGF)-β1.The Journal of biological chemistry · 2014Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phagocytosis occurs primarily through two main processes in macrophages: the Fcγ receptor- and the integrin αMβ2-mediated processes. Complement C3bi-opsonized particles are known to be engulfed through integrin αMβ2-mediated process, which is regulated by RhoA GTPase. C3 toxin fused with Tat-peptide (Tat-C3 toxin), an inhibitor of the Rho GTPases, was shown to markedly inhibit the phagocytosis of serum (C3bi)-opsonized zymosans (SOZs). However, 8CPT-2Me-cAMP, an activator of exchange protein directly activated by cAMP (Epac, Rap1 guanine nucleotide exchange factor), restored the phagocytosis of the SOZs that was previously inhibited by the Tat-C3 toxin. In addition, a constitutively active form of Rap1 GTPase (CA-Rap1) also restored the phagocytosis that was previously reduced by a dominant negative form of RhoA GTPase (DN-RhoA). This suggests that Rap1 can replace the function of RhoA in the phagocytosis. Inversely, CA-RhoA rescued the phagocytosis that was suppressed by DN-Rap1. These findings suggest that both RhoA and Rap1 GTPases collectively regulate the phagocytosis of SOZs. In addition, filamentous actin was reduced by the Tat-C3 toxin, which was again restored by 8CPT-2Me-cAMP. Small interfering profilin suppressed the phagocytosis, suggesting that profilin is essential for the phagocytosis of SOZs. Furthermore, 8CPT-2Me-cAMP increased the co-immunoprecipitation of profilin with Rap1, whereas Tat-C3 toxin decreased that of profilin with RhoA. Co-immunoprecipitations of profilin with actin, Rap1, and RhoA GTPases were augmented in the presence of GTPγS rather than GDP. Therefore, we propose that both Rap1 and RhoA GTPases regulate the formation of filamentous actin through the interaction between actin and profilin, thereby collectively inducing the phagocytosis of SOZs in macrophages.
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