Isoform-Specific Membrane Targeting Mechanism of Rac during FcγR-Mediated Phagocytosis: Positive Charge-Dependent and Independent Targeting Mechanism of Rac to the Phagosome
Open accessAbstract
Rac1 and Rac2 are capable of stimulating superoxide production in vitro, but their targeting and functional mechanisms are still unknown. In the present study, we found that Rac1, 2, and 3 all accumulate at the phagosome during FcγR-mediated phagocytosis, and that the order of accumulation (Rac1 > Rac3 > Rac2) depends on the net positive charge in their polybasic (PB) regions (183–188 aa). Although all GFP-tagged prenylated PB regions of Rac isoforms (GFP-Rac(PB)) and GFP-tagged prenylated 6 Ala (GFP-6A) accumulated during phagocytosis, GFP-Rac2(PB) and GFP-6A showed weak accumulation at the phagosome through a linear structure connecting the phagosome and endomembranes. The PB region of Rac1 showed strong phospholipid interaction with PI(3)P, PI(4)P, PI(5)P, PI(3,4,5)P3, and phosphatidic acid, however, that of Rac2 did not. Constitutively active Rac2, GFP-Rac2(Q61L), was predominantly localized at the endomembranes; these endomembranes fused to the phagosome through the linear structure during phagocytosis, and this accumulation mechanism did not depend on positive charge in the PB region. Our conclusion is that Rac1 directly targets to the phagosome using the positively charged PB region and this accumulation mechanism is likely enhanced by the phospholipids. In addition to this mechanism, Rac2 has a positive charge-independent mechanism in which Rac2 initially targets to endomembranes and then these endomembranes fuse to the phagosome.
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- Authors
- Ueyama, T., Eto, M., Kami, K., Tatsuno, T., Kobayashi, T., Shirai, Y., Lennartz, M. R., Takeya, R., Sumimoto, H., & Saito, N.
- Affiliations
- Biosignal Research Center, Kobe University (JP)
- Kyushu University (JP)
- University of Kochi (JP)
- Albany Medical College (US)
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-08
- Volume
- 175
- Issue
- 4
- Pages
- 2381-2390
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2143045155
- Cited by
- 50
- References
- 49
- Citations by year
- 2025: 1 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 3 · 2015: 1 · 2014: 1 · 2013: 1 · 2012: 1
- FWCI
- 1.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- Rac1, Rac2, RAC3, phagosome, membrane targeting, polybasic region, positive charge, phospholipid interactions, phosphoinositides, superoxide production, neutrophils
- MeSH terms
- RAC2 GTP-Binding Protein, Animals, Binding Sites, Cell Line, Cell Membrane, Cell-Free System, Isoenzymes, Macrophages, Peptide Fragments, Phagocytosis, Phagosomes, Phospholipids, Superoxides, Protein Prenylation, Protein Structure, Tertiary, Receptors, IgG, rac GTP-Binding Proteins, rac1 GTP-Binding Protein, Amino Acids, Basic, Mutant Chimeric Proteins, Mice, Static Electricity
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